Repositório Institucional - Unifesp :: Navegando por Palavras-chave "insulin"

Navegando por Palavras-chave "insulin"

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Acesso aberto (Open Access)
Abnormal nocturnal blood pressure fall in normotensive adolescents with insulin-dependent diabetes is ameliorated following glycemic improvement
(Associação Brasileira de Divulgação Científica, 1998-04-01) Ferreira, Sandra Roberta Gouvea [UNIFESP]; Cesarini, Paulo Roberto [UNIFESP]; Vivolo, Mariana Aun; Zanella, Maria Teresa [UNIFESP]; A01; Universidade Federal de São Paulo (UNIFESP)
Lack of the physiological nocturnal fall in blood pressure (BP) has been found in diabetics and it seems to be related to the presence of diabetic complications. The present study examined the changes in the nocturnal BP pattern of 8 normotensive insulin-dependent diabetic adolescents without nephropathy following improvement in glycemic control induced by an 8-day program of adequate diet and exercise. The same number of age- and sex-matched control subjects were studied. During the first and eighth nights of the program, BP was obtained by ambulatory BP monitoring. After a 10-min rest, 3 BP and heart rate (HR) recordings were taken and the mean values were considered to represent their awake values. The monitor was programmed to cuff insufflation every 20 min from 10:00 p.m. to 7:00 a.m. The glycemic control of diabetics improved since glycemia (212.0 ± 91.5 to 140.2 ± 69.1 mg/dl, P<0.03), urine glucose (12.7 ± 11.8 to 8.6 ± 6.4 g/24 h, P = 0.08) and insulin dose (31.1 ± 7.7 to 16.1 ± 9.7 U/day, P<0.01) were reduced on the last day. The mean BP of control subjects markedly decreased during the sleeping hours of night 1 (92.3 ± 6.4 to 78.1 ± 5.0 mmHg, P<0.001) and night 8 (87.3 ± 6.7 to 76.9 ± 3.6 mmHg, P<0.001). Diabetic patients showed a slight decrease in mean BP during the first night. However, the fall in BP during the nocturnal period increased significantly on the eighth night. The average awake-sleep BP variation was significantly higher at the end of the study (4.2 vs 10.3%, P<0.05) and this ratio turned out to be similar to that found in the control group (10.3 vs 16.3%). HR variation also increased on the eighth night in the diabetics. Following the metabolic improvement obtained at the end of the period, the nocturnal BP variation of diabetics was close to the normal pattern. We suggest that amelioration of glycemic control may influence the awake-sleep BP and HR differences. This effect may be due at least in part to an attenuated insulin stimulation of sympathetic activity
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Are Major Depressive Disorder and Diabetes Mellitus Amyloidogenic Conditions?
(Bentham Science Publ Ltd, 2014-01-01) Baskaran, Anusha; Carvalho, Andre F.; Mansur, Rodrigo Barbachan [UNIFESP]; McIntyre, Roger S.; Queens Univ; Univ Hlth Network; Univ Fed Ceara; Universidade Federal de São Paulo (UNIFESP); Univ Toronto
Major depressive disorder (MDD) and diabetes mellitus (DM) have reciprocal relationship and share common pathophysiological mechanisms in the central nervous system. Depression and diabetes negatively affect cognitive function and are independent risk factors for mild cognitive impairment and Alzheimers disease (AD). It has been hypothesized that alterations in the production and processing of amyloid beta (A beta) may be the principal pathological process in AD. Furthermore, it has been increasingly demonstrated that a long preclinical course precedes AD. A derivative of this observation is the hypothesis that a convergent pathophysiological substrate subserving MDD and DM may promote beta amyloid (A beta) deposition. The present paper will review evidence linking MDD and DM to A beta accumulation, with a particular emphasis on original reports that report on levels of A beta 40, A beta 42 and the A beta 40/42 ratio in plasma, serum, or cerebrospinal fluid of individuals with MDD and DM. The overarching goal herein is to press the point that MDD and DM are amyloidogenic and consequently represent modifiable risk factors for AD in later life. The prognostic intervention and prevention opportunity suggested by this notion is that: 1) increased rates of mood disorders and DM in an aging population will increase the population attributable risk for AD ascribed to these conditions, 2) improved outcomes in mood disorders and DM by effective treating to target may exert a salutary influence on underlying dementia promoting processes, 3) novel and repurposed medications that are capable of normalizing pathophysiological processes in MDD and DM could decrease the vulnerability towards AD.
Acesso aberto (Open Access)
Avaliação da expressão gênica das vias de sinalização de insulina em células da granulosa provenientes de mulheres eutróficas e obesas com síndrome dos ovários policísticos em ciclos de fertilização in vitro
(Universidade Federal de São Paulo (UNIFESP), 2015-11-27) Chehin, Mauricio Barbour [UNIFESP]; Motta, Eduardo Leme Alves da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Objective: To evaluate granulosa cell gene expression from insulin signaling pathway of Polycystic Ovarian Syndrome (PCOS) patients after In Vitro Fertilization (IVF) and compare the granulosa gene expression activity between eutrophic and obese women. Methods: Cross-sectional study with 15 PCOS patients, nine eutrophic and six obese, which were submitted to oocyte recovery to IVF and after the procedure had the granulosa cumulus cells removed from the oocyte to RNA extraction and later quantitative PCR array analysis of expression gene profile. The results were expressed by fold up or fold down of obese patients gene expression over eutrophic patients gene expression, fold ? 3 or ? 3 values and p ? 0,05 were considered statiscally significant. Results: The analyzed genes are overexpressed in obese compared to eutrophic women. There are 09 genes, BCL2L1, BRAF, CBL, DOK1, FBP1, FRS2, PCK2, RPS6KA1 and SORBS1 that presents fold ? 3 and p ? 0,05. Conclusions: In the group OB significantly overexpressed genes are responsible for the proliferation and differentiation of cumulus cells during oocyte maturation, insulin resistance, regulation of apoptosis, and glucose metabolism during early embryogenesis.
Acesso aberto (Open Access)
Blood glucose and insulin levels in patients with peripheral vestibular disease
(Associação Brasileira de Otorrinolaringologia e Cirurgia Cervicofacial, 2009-10-01) Serra, Ana Paula; Lopes, Karen de Carvalho [UNIFESP]; Dorigueto, Ricardo Schaffeln [UNIFESP]; Ganança, Fernando Freitas [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Metabolic disorders can cause dizziness. AIM: to study the prevalence of glucose and glucose-insulin alterations in patients with peripheral vestibular disorders by studying the four-hour glucose-insulin curve; to check at what time there was the highest prevalence of altered cases and whether the glucose and insulin curves together are better than the isolate glucose curve and fasting glucose curve. MATERIALS AND METHODS: retrospective study, analyzing 81 four-hour glucose-insulin curves in patients with peripheral vestibular dizziness. RESULTS: Four-hour glucose-insulin curve alterations happened in 87.7% of the patients. Hypoglycemia was seen in 61.7% of the cases, hyperinsulinemia in 55.5%, hyperglycemia in 27.2%, glucose intolerance in 12.3% and hypoinsulinemia in 1.2%. Normal tests were seen in 12.3 % of the cases and altered fasting glucose in 23.5%. CONCLUSIONS: The four-hour glucose-insulin curve analysis showed that 87.7% of the patients with dizziness and suspicion of peripheral vestibular disorder had glucose or insulin metabolism disorders. The highest number of alterations was seen up to the third and fourth hour of the glucose-insulin curve. The glucose and insulin curves together overcame the glucose curve alone and fasting glucose curve in regards of the prevalence of altered cases.
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Effect of long-term type 1 diabetes on renal sodium and water transporters in rats
(Karger, 2008-01-01) Vidotti, Daniela B. [UNIFESP]; Arnoni, Carine P. [UNIFESP]; Maquigussa, Edgar [UNIFESP]; Boim, Mirian A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
The effects of long-term diabetes in the presence of established nephropathy on tubular function remains poorly understood. We evaluated the levels of the main sodium and water transport proteins expressed in the kidney after long-term (8 weeks) of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) in untreated (D) and insulin (4 U/s.c./day)-treated (D+I) rats. D animals presented upregulation (similar to 4.5-fold) of Na/ glucose cotransporter (SGLT1), whereas the alpha-subunit of the epithelial sodium channel (alpha-ENaC) and aquaporin 1 (AQP1) were downregulated (similar to 20 and 30% respectively) with no change in the Na/H exchanger (NHE3), Na/Cl cotransporter (TSC) and AQP2. Insulin replacement partially prevented these alterations and caused increases in the expression of alpha-ENaC and AQP2. These effects suggest an action of insulin in the tubular transport properties. the upregulation of SGLT1 may constitute a mechanism to prevent greater glucose losses in the urine but it may result in glucotoxicity to the proximal epithelial cells contributing to the diabetic nephropathy. the decrease of alpha-ENaC in D animals may compensate for the increased sodium reabsorption via SGLT1 resulting in discrete natriuresis. DM-induced polyuria was not due to changes in AQP2 expression. Copyright (c) 2007 S. Karger AG, Basel.
Acesso aberto (Open Access)
Elaboração e implementação de protocolo de controle glicêmico em pacientes não críticos hospitalizados em hospital terciário
(Universidade Federal de São Paulo (UNIFESP), 2016-07-27) Carpentieri, Giovanna Braganholo [UNIFESP]; Sa, Joao Roberto de Sa [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Introduction: Hyperglycemia in diabetic and non-diabetic patients hospitalized in noncritically ill condition is common in general hospitals. Several observational studies with inpatients show a strong correlation between hyperglycemia and increased risk of adverse clinical outcomes, such as prolonged hospitalization, higher infections rates, increased morbidity and mortality and increased hospital costs. Although current guidelines recommend that hyperglycemic patients should be treated with basal-bolus insulin regimen, a more physiological and effective method, in most hospitals it still prevails the use of the sliding scale, treatment associated with increased glycemic variability and poor prognosis. Purpose: Develop and implement an institutional protocol for glycemic control in noncritically ill inpatients. Methods: The study was conducted at Hospital São Paulo of the Paulista School of Medicine - Federal University of São Paulo. The project was developed in three phases. The first phase consisted of the theoretical foundation and development of a pilot protocol according to the current guidelines and based on existing protocols at other institutions. In the second phase, meetings were held with the Clinical and Technical Directors and with the management teams of nutrition, laboratory and nursing to adapt the pilot protocol to the needs and technical and human conditions of the hospital. The last phase was based on an outreach program for the professionals involved in the inpatients care. Results: a protocol for glycemic control for noncritically ill patients customized according to the complexity and the material and human resources of the Hospital São Paulo was prepared. The protocol was designed in the form of flow charts, one for the treatment of hyperglycemia, using the basal-bolus insulin therapy regimen, and a second one for the treatment of hypoglycemia. It was approved by the board of the Hospital São Paulo. The outreach plan included training of professionals involved in the care of hospitalized patients through printed materials, lectures and teaching materials available on the Internet. After training, the project was implemented in 30 medical and surgical wards of the institution. Conclusion: The development and implementation of an institutional protocol for glycemic control is a potentially effective way to increase security by treating hyperglycemic patients and improve the quality of care provided by health professionals. This deployment model can guide other hospitals in their initiatives for the management of blood glucose levels in hospitalized patients.
Acesso aberto (Open Access)
A evolução da insulinoterapia no diabetes melito tipo 1
(Sociedade Brasileira de Endocrinologia e Metabologia, 2008-03-01) Pires, Antonio Carlos; Chacra, Antonio Roberto [UNIFESP]; Faculdade de Medicina de São José do Rio Preto; Universidade Federal de São Paulo (UNIFESP)
The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells.
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Is insulin or its precursor independently associated with hypertension? An epidemiological study in Japanese-Brazilians
(Amer Heart Assoc, 1997-09-01) Ferreira, Sandra Roberta Gouvea [UNIFESP]; Franco, Laercio Joel [UNIFESP]; Gimeno, Suely Godoy Agostinho [UNIFESP]; Iochida, Lucia Christina [UNIFESP]; Iunes, Magid [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Japanese individuals living outside Japan are more susceptible to chronic diseases included in the insulin resistance syndrome. Hyperinsulinemia and hypertension are associated, but large studies adjusting for confounders are still required. The present evaluated if insulin (I) or proinsulin (PI) was associated with hypertension after adjustment for other risk factors, in first (n=238) and second (n=292) generation Japanese-Brazilians, aged 40 to 79 years, living in a developed city in Brazil. Blood pressure (BP) was measured by random-zero sphygmomanometry. People with mean systolic/diastolic BP >140/90 mm Hg or taking antihypertensive drugs were considered hypertensive. Diagnosis of diabetes was based on results of an oral glucose tolerance test using WHO criteria. I and PI after fasting and 2 hours after glucose load were determined by specific immunofluorimetric assays. The first generation was older than the second (65.6+/-9.2 versus 53.6+/-8.4 years, P<.01) and male/female ratios were 1.14 and 0.87, respectively. The age-adjusted prevalence of hypertension was 29.2% with no difference between sexes or generations. Higher body mass index (25.2+/-4.3 versus 23.8+/-3.3 kg/m(2)), waist-to-hip ratio (0.939+/-0.067 versus 0.919+/-0.073), plasma glucose (6.3+/-2.3 versus 5.6+/-1.8 mmol/L), cholesterol (5.74+/-1.19 versus 5.48+/-1.08 mmol/L), and creatinine (74+/-26 versus 83+/-36 mu mol/L) were found among the hypertensives (P<.05). Univariate analyses showed associations of obesity, diabetes, and dyslipidemia with hypertension. Logistic regression analyses demonstrated that 2-hour I (OR, 1.22; 95% CI, 1.02 to 1.46) and fasting PI (OR, 1.14; 95% CI, 1.00 to 1.31) remained significantly associated with hypertension, after adjustment for age, sex, generation, family history of hypertension, smoking habits, waist-to-hip ratio, serum creatinine, glucose intolerance, and dyslipidemia. Japanese-Brazilians have a higher prevalence of hypertension than the general population in Brazil. High levels of 2-hour I, seen in hypertensives, may be interpreted as independent risk factors for hypertension in this population. Our findings suggest that fasting PI should be useful, in addition to insulin, to assess risk factors for hypertension in epidemiological studies.
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Kinin B-1 receptor stimulation modulates leptin homeostasis. Evidence for an insulin-dependent mechanism
(Elsevier B.V., 2008-02-01) Mori, Marcelo A. [UNIFESP]; Araujo, Ronaldo C. [UNIFESP]; Pesquero, Joao B. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Kinins are potent vasoactive and inflammatory peptides generated by kallikreins in blood and tissues that bind to specific receptors named B-1 and B-2. On the other hand, leptin is an adipocytokine that displays broad effects on energy balance, inflammation and vascular tone. Here we demonstrate that the intravenous administration of the kinin B-1 receptor agonist des-Arg(9)-bradykinin (DBK) in mice leads to significant increase in serum leptin levels. However, incubation of isolated white adipose tissue with DBK was not sufficient to induce leptin release or leptin mRNA overexpression. On the contrary, long-term DBK treatment in isolated fat tissue impaired insulin-mediated actions on leptin secretion and expression. in order to verify whether the in vivo effect of B-1 receptor stimulation on leptin release was also dependent on blood insulin levels, DBK was injected in animals in hyperinsulinemic state. in this case, however, DBK was not able to potentiate leptinemia. Therefore, our results show that the B-1 receptor stimulation may modulate leptin homeostasis in an insulin-dependent manner. These new findings contribute to a better understanding of the processes involving leptin regulation and highlight the involvement of kinins with metabolic processes. (c) 2007 Elsevier B.V. All rights reserved.
Acesso aberto (Open Access)
Long-Lasting Effects of Undernutrition
(Mdpi Ag, 2011-06-01) Martins, Vinicius José Baccin [UNIFESP]; Toledo Florencio, Telma M. M.; Grillo, Luciane P.; Franco, Maria do Carmo Pinho [UNIFESP]; Martins, Paula Andrea [UNIFESP]; Clemente, Ana Paula Grotti [UNIFESP]; Santos, Carla Danusa da Luz [UNIFESP]; Vieira, Maria de Fatima Alves; Sawaya, Ana Lydia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Alagoas; Vale Itajai Univ; Univ Fed Pelotas
Undernutrition is one of the most important public health problems, affecting more than 900 million individuals around the World. It is responsible for the highest mortality rate in children and has long-lasting physiologic effects, including an increased susceptibility to fat accumulation mostly in the central region of the body, lower fat oxidation, lower resting and postprandial energy expenditure, insulin resistance in adulthood, hypertension, dyslipidaemia and a reduced capacity for manual work, among other impairments. Marked changes in the function of the autonomic nervous system have been described in undernourished experimental animals. Some of these effects seem to be epigenetic, passing on to the next generation. Undernutrition in children has been linked to poor mental development and school achievement as well as behavioural abnormalities. However, there is still a debate in the literature regarding whether some of these effects are permanent or reversible. Stunted children who had experienced catch-up growth had verbal vocabulary and quantitative test scores that did not differ from children who were not stunted. Children treated before 6 years of age in day-hospitals and who recovered in weight and height have normal body compositions, bone mineral densities and insulin production and sensitivity.
Acesso aberto (Open Access)
Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic ß-cell demand in men
(Associação Brasileira de Divulgação Científica, 1998-12-01) Reis, André Fernandes [UNIFESP]; Miranda, Walkiria Lopes [UNIFESP]; Chacra, Antonio Roberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic ß-cell demand (e.g. obesity) both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic ß-cell secretion in men with different body compositions. Eighteen young men (30.0 ± 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P<0.05), proinsulin (r = -0.47, P<0.05), C-peptide (r = -0.55, P<0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P<0.05). Stepwise regression analysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P<0.05). When subjects were divided into obese (BMI >28 kg/m2, N = 8) and nonobese (BMI £25 kg/m2, N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic ß-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic ß-cell demand.
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Melatonin improves insulin sensitivity independently of weight loss in old obese rats
(Wiley-Blackwell, 2013-09-01) Zanuto, Ricardo; Siqueira-Filho, Mario A.; Caperuto, Luciana C. [UNIFESP]; Bacurau, Reury Frank Pereira; Hirata, Emiko [UNIFESP]; Peliciari-Garcia, Rodrigo A.; Amaral, Fernanda Gaspar do; Marcal, Anderson C.; Ribeiro, Luciene M.; Camporez, Joao P. G.; Carpinelli, Angelo Rafael; Bordin, Silvana; Cipolla-Neto, Jose; Carvalho, Carla R. O.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
In aged rats, insulin signaling pathway (ISP) is impaired in tissues that play a pivotal role in glucose homeostasis, such as liver, skeletal muscle, and adipose tissue. Moreover, the aging process is also associated with obesity and reduction in melatonin synthesis from the pineal gland and other organs. the aim of the present work was to evaluate, in male old obese Wistar rats, the effect of melatonin supplementation in the ISP, analyzing the total protein amount and the phosphorylated status (immunoprecipitation and immunoblotting) of the insulin cascade components in the rat hypothalamus, liver, skeletal muscle, and periepididymal adipose tissue. Melatonin was administered in the drinking water for 8- and 12 wk during the night period. Food and water intake and fasting blood glucose remained unchanged. the insulin sensitivity presented a 2.1-fold increase both after 8- and 12 wk of melatonin supplementation. Animals supplemented with melatonin for 12 wk also presented a reduction in body mass. the acute insulin-induced phosphorylation of the analyzed ISP proteins increased 1.3- and 2.3-fold after 8- and 12 wk of melatonin supplementation. the total protein content of the insulin receptor (IR) and the IR substrates (IRS-1, 2) remained unchanged in all investigated tissues, except for the 2-fold increase in the total amount of IRS-1 in the periepididymal adipose tissue. Therefore, the known age-related melatonin synthesis reduction may also be involved in the development of insulin resistance and the adequate supplementation could be an important alternative for the prevention of insulin signaling impairment in aged organisms.
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Metabolic profile and cardiovascular risk patterns of an Indian tribe living in the Amazon Region of Brazil
(Wayne State Univ Press, 2003-02-01) Tavares, E. F.; Vieira, JPB; Andriolo, A.; Sanudo, A.; Gimeno, SGA; Franco, L. J.; Universidade Federal de São Paulo (UNIFESP)
The Parkateje Indians, belonging to the Je group and inhabiting the Mae Maria Reservation in the southeast of the state of Para in the Amazon Region of Brazil, have suffered rapid and intensive cultural changes in recent years. This survey was designed to characterize the metabolic profile and the frequency of cardiovascular risk factors in this community. Ninety subjects (90.0% of the adult population without admixture) were investigated. Anthropometric measurements were performed and the following clinical characteristics measured: glycemia, serum insulin and proinsulin (fasting and 2-hr post 75 g of glucose load), beta-cell function (%B) and insulin sensitivity (%S) estimated by HOMA, HbA1c, GAD65 antibody, serum lipids, uric acid, creatinine, leptin, and blood pressure. Information about alcohol use, smoking, and medical history was obtained through individual interviews. the prevalences were: overweight, 67.8%; obesity, 14.4%; central obesity, 72.2%; hypertension, 4.4%; dyslipidemia, 44.4%; hyperuricemia, 5.6%; GAD65 antibody positivity, 4.4%; smoking, 25.6%; chronic alcohol use, 0.0%. One case of impaired glucose tolerance (1.1%) and one case of impaired fasting glycemia (1.1%) were diagnosed during this study and one case of diabetes (1.1%) was diagnosed previously. the diabetic woman was excluded from the analyses involving HbA1c, glycemia, insulin, proinsulin, %B, and %S. All creatinine values were normal. Blood pressure did not correlate with age, anthropometric measurements, insulin, proinsulin, and natural logarithm (In) transformed %S. After adjustment for age and sex, there were positive correlations between total cholesterol and body mass index (BMI; r = 0.24), triglycerides and BMI (r = 0.44), triglycerides and waist-to-hip ratio (WHR; r = 0.52), in leptin and BMI (r = 0.41), in leptin and WHR (r = 0.29), uric acid and systolic blood pressure (r = 0.34), uric acid and triglycerides (r = 0.22). Systolic (r = 0.04; r = 0.70) and diastolic (r = 0.14; p = 0.18) blood pressure did not correlate with BMI. Ln leptin had a weak positive correlation with 2-hr insulin (r = 0.14) adjusted for age, sex, and BMI. the multiple linear regression model containing the variables sex, BMI, and 2-hr insulin concentrations explained 77.2% of the variation of in leptin. in conclusion, the high rates of cardiovascular risk factors found among these Indians point to there being a high-risk group to develop diabetes and cardiovascular diseases. To reduce this risk they need to receive preventive interventions.
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Modulation of IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of MSG-rats
(Elsevier B.V., 2003-08-01) Hirata, A. E.; Alvarez-Rojas, F.; Carvalheira, JBC; Carvalho, CRD; Dolnikoff, M. S.; Saad, MJA; Universidade Estadual de Campinas (UNICAMP); Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
PTP1B has been shown to be a negative regulator of the insulin signal transduction in insulin resistant states. Herein we investigated IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of 10 and 28-week-old MSG-insulin resistant rats which represent different stages of insulin resistance. Our results demonstrated that the increase in PTP1B expression and/or association with IR in MSG animals may contribute to the impaired insulin signaling mainly in liver and muscle. Although, adipose tissue of 10-week-old MSG rats showed higher PTP1B expression and IR/PTP1B interaction, they were not sufficient to impair all insulin signaling since IRS-2 phosphorylation and association with PI3-kinase and Akt serine phosphorylation were increased, which may contribute for the increased adiposity of these animals. in 28-week-old-MSG rats there was an increase in IR/PTP1B interaction and reduced insulin signaling in liver, muscle and adipocytes, and a more pronounced insulin resistance. (C) 2003 Elsevier Science Inc. All rights reserved.
Acesso aberto (Open Access)
Nutritional recovery with rice bran did not modify energy balance and leptin and insulin levels
(Sociedade Brasileira de Endocrinologia e Metabologia, 2010-03-01) Martins, Maria Salete F.; Oyama, Lila Missae [UNIFESP]; Latorraca, Marcia Q.; Gomes-da-Silva, Maria Helena G.; Nascimento, Claudia Maria da Penha Oller do [UNIFESP]; Universidade Federal de Mato Grosso Faculdade de Nutrição; Universidade Federal de São Paulo (UNIFESP)
OBJECTIVE: To investigate the effect of nutritional recovery with rice bran on energy balance, leptin and insulin levels. METHODS: Weaned Wistar rats were fed on a 17% (Control - C) or 0.5% (Aproteic - A) protein diet for 12d. After this, rats were kept on a C diet (C) or recovered with control (Recovered Control - RC) or control plus recovered rice bran diet (Recovered Rice Bran - RRB). RESULTS: Despite the increased food intake, group A exhibited lower carcass fat associated to low serum leptin. RRB and RC groups showed lower carcass weight and energy intake and expenditure. Energy expenditure was positively associated with food intake and carcass weight. Negative correlations between HOMA-IR and energy expenditure and energy intake were observed. CONCLUSION: Nutritional recovery with rice bran did not modify energy balance, leptin and insulin levels.
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Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation
(Amer Physiological Soc, 2010-03-01) Forcina Martins, Paulo Jose [UNIFESP]; Marques, Marina Soares [UNIFESP]; Tufik, Sergio [UNIFESP]; D'Almeida, Vania [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Martins PJ, Marques MS, Tufik S, D'Almeida V. Orexin activation precedes increased NPY expression, hyperphagia, and metabolic changes in response to sleep deprivation. Am J Physiol Endocrinol Metab 298: E726-E734, 2010. First published January 5, 2010; doi:10.1152/ajpendo.00660.2009.-Several pieces of evidence support that sleep duration plays a role in body weight control. Nevertheless, it has been assumed that, after the identification of orexins (hypocretins), the molecular basis of the interaction between sleep and energy homeostasis has been provided. However, no study has verified the relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia induced by sleep deprivation. in the current study we aimed to establish the time course of changes in metabolite, endocrine, and hypothalamic neuropeptide expression of Wistar rats sleep deprived by the platform method for a distinct period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite changes in the stress hormones, we found no changes in food intake and body weight in the SR-21d group. However, sleep-deprived rats had a 25-35% increase in their food intake from 72 h accompanied by slight weight loss. Such changes were associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced the expression of both PPO and NPY, which rapidly brought the animals to a hypophagic condition. Our data also support that sleep deprivation rapidly increases energy expenditure and therefore leads to a negative energy balance and a reduction in liver glycogen and serum triacylglycerol levels despite the hyperphagia. Interestingly, such changes were associated with increased serum levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin, insulin, or ghrelin were observed. in conclusion, orexin activation accounts for the myriad changes induced by sleep deprivation, especially the hyperphagia induced under stress and a negative energy balance.
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Proinsulin and insulin levels according to glucose tolerance among Japanese-Brazilians, aged 40-79 years
(Elsevier B.V., 1996-10-01) Iochida, Lucia Christina [UNIFESP]; Marcopito, Luiz Francisco [UNIFESP]; Franco, Laercio Joel [UNIFESP]; Ferreira, Sandra Roberta Gouvea [UNIFESP]; Iunes, Magid [UNIFESP]; Dalbosco, Ivaldir Sabino [UNIFESP]; Russo, Ewaldo Mario Kuhlmann [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); UNIV FED RIO GRANDE
This study of the Japanese-Brazilians living in Bauru, Sao Paulo, Brazil, aimed at determining the prevalence of DM in the first (Issei) and second (Nisei) generations, according to WHO criteria. Insulin and proinsulin were determined by new immunofluorimetric assays (IMFA), that, measure true insulin and intact proinsulin, at fasting and 2 h after glucose load. The data showed a very scattered distribution, so only medians are shown and no statistical testing applied. There was a tendency for higher fasting proinsulin levels in the diabetic groups. The highest fasting proinsulin levels were seen in the diabetic patients, Either obese or non-obese. The post-load insulin levels were higher in diabetic and IGT individuals, compared to normals. Both generations showed a distinct behaviour for the obese and non-obese groups. and no major differences were observed between generations. This population seems to be sensitive to environmental changes, since the obese groups showed the higher levels of proinsulin and insulin. In the evaluation of the role of the environmental factors in the pathogenesis of DM, proinsulin and insulin levels could act as early markers of pancreatic dysfunctions.
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Regulation of Glucose Uptake in Mesangial Cells Stimulated by High Glucose: Role of Angiotensin II and Insulin
(Soc Experimental Biology Medicine, 2009-09-01) Arnoni, Carine P. [UNIFESP]; Lima, Carla [UNIFESP]; Cristovam, Priscila C. [UNIFESP]; Maquigussa, Edgar [UNIFESP]; Vidotti, Daniela B. [UNIFESP]; Boim, Mirian A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Mesangial cells (MCs) play a central role in the pathogenesis of diabetic nephropathy (DN). MC dysfunction arises from excessive glucose uptake through insulin-independent glucose transporter (GLUT1). the role of the insulin-dependent transporter (GLUT4) remains unknown. This study evaluated the effect of high glucose on GLUT1, GLUT4, and fibronectin expression levels. Glucose uptake was determined in the absence and presence of insulin. Angiotensin 11 has been implicated as a mediator of MC abnormalities in DN, and its effects on the GLUTs expression were evaluated in the presence of losartan. MCs were exposed to normal (NG, 10 mM) or high (HG, 30 mM) glucose for 1, 4,12, 24 and 72 hrs. Glucose uptake was elevated from 1 hr up to 24 hrs of HG, but returned to NG levels after 72 hrs. HG induced an early (1-, 4-, and 12-hrs) rise in GLUT1 expression, returning to NG levels after 72 hrs, whereas GLUT4 was overexpressed at later timepoints (24 and 72 hrs). HG during 4 hrs induced a 40% rise in glucose uptake, which was unaffected by insulin. in contrast, after 72 hrs, glucose uptake was increased by 5006, only under insulin stimulus. Losartan blunted the effects of HG on GLUT1, GLUT4, and fibronectin expression and on glucose uptake. Results suggest that MCs can be highly susceptible to the HG environment since they uptake glucose in both an insulin-independent and insulin-dependent manner. the beneficial effects of angiotensin 11 inhibition in DN may also involve a decrease in the rate of glucose uptake by MCs. Exp Biol Med 234:1095-1101, 2009
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Role of the kinin B-1 receptor in insulin homeostasis and pancreatic islet function
(Walter de Gruyter & Co, 2006-04-01) Araujo, R. C.; Mori, M. A.; Merino, V. F.; Bascands, J. L.; Schanstra, J. P.; Zollner, R. L.; Villela, C. A.; Nakaie, C. R.; Paiva, ACM; Pesquero, J. L.; Bader, M.; Pesquero, J. B.; Universidade Federal de São Paulo (UNIFESP); Univ Mogi Cruzes; CHU Rangueil; Universidade Estadual de Campinas (UNICAMP); Max Delbruck Ctr Mol Med
Kinins are potent vasoactive peptides generated in blood and tissues by the kallikrein serine proteases. Two distinct kinin receptors have been described, one constitutive subtype B-2) and one inducible (subtype B-1), and many physiological functions have been attributed to these receptors, including glucose homeostasis and control of vascular permeability. in this study we show that mice lacking the kinin B-1 receptor (B-1(-/-) mice) have lower fasting plasma glucose concentrations but exhibit higher glycemia after feeding when compared to wild-type mice. B-1(-/-) mice also present pancreas abnormalities, characterized by fewer pancreatic islets and lower insulin content, which leads to hypoinsulinemia and reduced insulin release after a glucose load. Nevertheless, an insulin tolerance test indicated higher sensitivity in B-1(-/-) mice. in line with this phenotype, pancreatic vascular permeability was shown to be reduced in B-1 receptor-ablated mice. the B-1 agonist desArg(9)bradykinin injected intravenously can induce the release of insulin into serum, and this effect was not observed in the B-1(-/-) mice or in isolated islets. Our data demonstrate the importance of the kinin B-1 receptor in the control of pancreatic vascular homeostasis and insulin release, highlighting a new role for this receptor in the pathogenesis of diabetes and related diseases.
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Specific insulin and proinsulin in normal glucose tolerant first-degree relatives of NIDDM patients
(Associação Brasileira de Divulgação Científica, 1999-01-01) Coifman, R. [UNIFESP]; Dalbosco, Ivaldir Sabino [UNIFESP]; Russo, E.m.k. [UNIFESP]; Moises, Regina Celia Mello Santiago [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
In order to identify early abnormalities in non-insulin-dependent diabetes mellitus (NIDDM) we determined insulin (using an assay that does not cross-react with proinsulin) and proinsulin concentrations. The proinsulin/insulin ratio was used as an indicator of abnormal ß-cell function. The ratio of the first 30-min increase in insulin to glucose concentrations following the oral glucose tolerance test (OGTT; I30-0/G30-0) was taken as an indicator of insulin secretion. Insulin resistance (R) was evaluated by the homeostasis model assessment (HOMA) method. True insulin and proinsulin were measured during a 75-g OGTT in 35 individuals: 20 with normal glucose tolerance (NGT) and without diabetes among their first-degree relatives (FDR) served as controls, and 15 with NGT who were FDR of patients with NIDDM. The FDR group presented higher insulin (414 pmol/l vs 195 pmol/l; P = 0.04) and proinsulin levels (19.6 pmol/l vs 12.3 pmol/l; P = 0.03) post-glucose load than the control group. When these groups were stratified according to BMI, the obese FDR (N = 8) showed higher fasting and post-glucose insulin levels than the obese NGT (N = 9) (fasting: 64.8 pmol/l vs 7.8 pmol/l; P = 0.04, and 60 min post-glucose: 480.6 pmol/l vs 192 pmol/l; P = 0.01). Also, values for HOMA (R) were higher in the obese FDR compared to obese NGT (2.53 vs 0.30; P = 0.075). These results show that FDR of NIDDM patients have true hyperinsulinemia (which is not a consequence of cross-reactivity with proinsulin) and hyperproinsulinemia and no dysfunction of a qualitative nature in ß-cells.

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