Navegando por Palavras-chave "Insulin secretion"

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    Bases Genéticas do Diabetes Mellitus Tipo 2
    (Sociedade Brasileira de Endocrinologia e Metabologia, 2002-08-01) Reis, André Fernandes [UNIFESP]; Velho, Gilberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The pathogenesis of type 2 diabetes mellitus (T2DM) is complex, but it is secondary to a combination of insulin resistance and pancreatic beta-cell dysfunction that manifests itself as inadequate insulin secretion in the face of hyperglycemia. Several studies have established a clear genetic predisposition for T2DM. Some genes for monogenic forms of diabetes have been identified (MODY, mitochondrial diabetes). However, few genes were found to be associated with diabetes in the more common forms of T2DM. In these T2DM forms, a variety of environmental factors play a major role in the clinical expression of disease. This article addresses the clinical and genetic advances in the genetic bases of T2DM.
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    Cholesterol reduction ameliorates glucose-induced calcium handling and insulin secretion in islets from low-density lipoprotein receptor, knockout mice
    (Elsevier B.V., 2013-04-01) Souza, J. C.; Vanzela, E. C.; Ribeiro, R. A.; Rezende, L. F.; Oliveira, Camila Aparecida Machado de [UNIFESP]; Carneiro, E. M.; Oliveira, H. C. F.; Boschero, A. C.; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP)
    Aims/hypothesis: Changes in cellular cholesterol level may contribute to beta cell dysfunction. Islets from low density lipoprotein receptor knockout (LDLR-/-) mice have higher cholesterol content and secrete less insulin than wild-type (WT) mice. Here, we investigated the association between cholesterol content, insulin secretion and Ca2+ handling in these islets.Methods: Isolated islets from both LDLR-/- and WT mice were used for measurements of insulin secretion (radioimmunoassay), cholesterol content (fluorimetric assay), cytosolic Ca2+ level (fura-2AM) and SNARE protein expression (VAMP-2, SNAP-25 and syntaxin-1A). Cholesterol was depleted by incubating the islets with increasing concentrations (0-10 mmol/l) of methyl-beta-cyclodextrin (M beta CD).Results: the first and second phases of glucose-stimulated insulin secretion (GSIS) were lower in LDLR-/- than in WT islets, paralleled by an impairment of Ca2+ handling in the former. SNAP-25 and VAMP-2, but not syntaxin-1A, were reduced in LDLR-/- compared with WT islets. Removal of excess cholesterol from LDLR-/- islets normalized glucose- and tolbutamide-induced insulin release. Glucose-stimulated Ca2+ handling was also normalized in cholesterol-depleted LDLR-/- islets. Cholesterol removal from WT islets by 0.1 and 1.0 mmol/l M beta CD impaired both GSIS and Ca2+ handling. in addition, at 10 mmol/l M beta CD WT islet showed a loss of membrane integrity and higher DNA fragmentation.Conclusion: Abnormally high (LDLR-/- islets) or low cholesterol content (WT islets treated with M beta CD) alters both GSIS and Ca2+ handling. Normalization of cholesterol improves Ca2+ handling and insulin secretion in LDLR-/- islets. (C) 2013 Elsevier B.V. All rights reserved.
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    Family History of Diabetes as a New Determinant of Insulin Sensitivity and Secretion in Patients Who Have Undergone a Simultaneous Pancreas-Kidney Transplant
    (Baskent Univ, 2010-03-01) Rangel, Erika Bevilaqua [UNIFESP]; Melaragno, Cláudio Santiago [UNIFESP]; Neves, Maria Deolinda F. [UNIFESP]; Dib, Sergio Atala [UNIFESP]; Gonzalez, Adriano Miziara [UNIFESP]; Linhares, Marcelo Moura [UNIFESP]; Pacheco-Silva, Alvaro [UNIFESP]; Sá, João Roberto de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objectives: We used homeostasis model assessment to investigate insulin sensitivity and secretion after a simultaneous pancreas-kidney transplant or kidney transplant alone. In that model, fasting plasma glucose and C-peptide levels are used to evaluate insulin sensitivity and beta-cell function.Materials and Methods: Factors (eg, age, sex, race, delayed kidney allograft function) were correlated with homeostasis model assessment of beta-cell function and homeostasis model assessment of insulin sensitivity values after simultaneous pancreas-kidney transplant (n=89) or kidney transplant alone (n=68), and the results were compared with those in healthy subjects (n=49).Results: Homeostasis model assessment of beta-cell function values were similar in patients who underwent kidney transplant alone or a simultaneous pancreas-kidney transplant, and were higher than homeostasis model assessment of beta-cell function values in healthy subjects. The homeostasis model assessment of insulin sensitivity showed intermediate values for patients who underwent a simultaneous pancreas-kidney transplant and correlated with prednisone dosages (in those who underwent kidney transplant alone) and tacrolimus levels (in patients who underwent a simultaneous pancreas-kidney transplant). Homeostasis model assessment of beta-cell function values correlated with prednisone dosages in both groups and with tacrolimus levels in only those who underwent a simultaneous pancreas-kidney transplant. The body mass index of subjects who underwent kidney transplant alone correlated with both homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results. A family history of diabetes in subjects who underwent a simultaneous pancreas-kidney transplant correlated with homeostasis model assessment of beta-cell function results and homeostasis model assessment of insulin sensitivity results.Conclusions: Immunosuppressive regimen and body mass index were linked with reduced insulin sensitivity after kidney transplant. A family history of diabetes was linked with higher values of insulin secretion and lower insulin sensitivity in patients who underwent a simultaneous pancreas-kidney transplant.
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    Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice
    (Amer Physiological Soc, 2012-07-01) Carvalho, Carolina Prado de França [UNIFESP]; Oliveira, R. B.; Britan, A.; Santos-Silva, J. C.; Boschero, A. C.; Meda, P.; Collares-Buzato, C. B.; Universidade Estadual de Campinas (UNICAMP); Univ Geneva; Universidade Federal de São Paulo (UNIFESP)
    Carvalho CP, Oliveira RB, Britan A, Santos-Silva JC, Boschero AC, Meda P, Collares-Buzato CB. Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice. Am J Physiol Endocrinol Metab 303: E144-E151, 2012. First published May 8, 2012; doi: 10.1152/ajpendo.00489.2011.-Gap junctional intercellular communication between beta-cells is crucial for proper insulin biosynthesis and secretion. the aim of this work was to investigate the expression of connexin (Cx) 36 at the protein level as well as the function and structure of gap junctions (GJ) made by this protein in the endocrine pancreas of prediabetic mice. C57BL/6 mice were fed a high-fat (HF) or regular chow diet for 60 days. HF-fed mice became obese and prediabetic, as shown by peripheral insulin resistance, moderate hyperglycemia, hyperinsulinemia, and compensatory increase in endocrine pancreas mass. Compared with control mice, prediabetic animals showed a significant decrease in insulin-secretory response to glucose and displayed a significant reduction in islet Cx36 protein. Ultrastructural analysis further showed that prediabetic mice had GJ plaques about one-half the size of those of the control group. Microinjection of isolated pancreatic islets with ethidium bromide revealed that prediabetic mice featured a beta-cell-beta-cell coupling 30% lower than that of control animals. We conclude that beta-cell-beta-cell coupling mediated by Cx36 made-channels is impaired in prediabetic mice, suggesting a role of Cx36-dependent cell-to-cell communication in the pathogenesis of the early beta-cell dysfunctions that lead to type 2-diabetes.
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    Mechanisms of insulin secretion in malnutrition: modulation by amino acids in rodent models
    (Springer, 2011-04-01) Oliveira, Camila Aparecida Machado de [UNIFESP]; Latorraca, Marcia Queiroz; Rostom de Mello, Maria Alice; Carneiro, Everardo Magalhaes; Universidade Estadual de Campinas (UNICAMP); Univ Fed Mato Grosso UFMT; Univ Estadual Paulista UNESP; Universidade Federal de São Paulo (UNIFESP)
    Protein restriction at early stages of life reduces beta-cell volume, number of insulin-containing granules, insulin content and release by pancreatic islets in response to glucose and other secretagogues, abnormalities similar to those seen in type 2 diabetes. Amino acids are capable to directly modulate insulin secretion and/or contribute to the maintenance of beta-cell function, resulting in an improvement of insulin release. Animal models of protein malnutrition have provided important insights into the adaptive mechanisms involved in insulin secretion in malnutrition. in this review, we discuss studies focusing on the modulation of insulin secretion by amino acids, specially leucine and taurine, in rodent models of protein malnutrition. Leucine supplementation increases insulin secretion by pancreatic islets in malnourished mice. This effect is at least in part due to increase in the expression of proteins involved in the secretion process, and the activation of the PI3K/PKB/mTOR pathway seems also to contribute. Mice supplemented with taurine have increased insulin content and secretion as well as increased expression of genes essential for beta-cell functionality. the knowledge of the mechanisms through which amino acids act on pancreatic beta-cells to stimulate insulin secretion is of interest for clinical medicine. It can reveal new targets for the development of drugs toward the treatment of endocrine diseases, in special type 2 diabetes.
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    Reduced insulin secretion function is associated with pancreatic islet redistribution of cell adhesion molecules (CAMs) in diabetic mice after prolonged high-fat diet
    (Springer, 2016) Falcao, Viviane Tannuri F. L.; Maschio, Daniela A.; Fontes, Camila Calvo de [UNIFESP]; Oliveira, Ricardo B.; Santos-Silva, Junia C.; Soares Almeida, Anna Carolina; Vanzela, Emerielle C.; Cartaxo, Maria Tereza; Carvalho, Carolina Prado de França [UNIFESP]; Collares-Buzato, Carla Beatriz
    Intercellular junctions play a role in regulating islet cytoarchitecture, insulin biosynthesis and secretion. In this study, we investigated the animal metabolic state as well as islet histology and cellular distribution/expression of CAMs and F-actin in the endocrine pancreas of C57BL/6/JUnib mice fed a high-fat diet (HFd) for a prolonged time period (8 months). Mice fed a HFd became obese and type 2 diabetic, displaying significant peripheral insulin resistance, hyperglycemia and moderate hyperinsulinemia. Isolated islets of HFd-fed mice displayed a significant impairment of glucose-induced insulin secretion associated with a diminished frequency of intracellular calcium oscillations compared with control islets. No marked change in islet morphology and cytoarchitecture was observed
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    Treatments for diabetes mellitus type II: New perspectives regarding the possible role of calcium and cAMP interaction
    (Elsevier Science Bv, 2018) Carvalho, Diego Soares [UNIFESP]; Almeida, Alexandre Aparecido de [UNIFESP]; Borges, Aurelio Ferreira; Campos, Vannucci [UNIFESP]
    Diabetes mellitus (DM) is among the top ten causes of death worldwide. It is considered to be one of the major global epidemics of the 21st century, with a significant impact on public health budgets. DM is a metabolic disorder with multiple etiologies. Its pathophysiology is marked by dysfunction of pancreatic beta-cells which compromises the synthesis and secretion of insulin along with resistance to insulin action in peripheral tissues (muscle and adipose). Subjects presenting insulin resistance in DM type 2 often also exhibit increased insulin secretion and hyperinsulinemia. Insulin secretion is controlled by several factors such as nutrients, hormones, and neural factors. Exocytosis of insulin granules has, as its main stimulus, increased intracellular calcium ([Ca+2] i) and it is further amplified by cyclic AMP (cAMP). In the event of this hyperfunction, it is very common for beta-cells to go into exhaustion leading to failure or death. Several animal studies have demonstrated pleiotropic effects of L-type Ca2+ channel blockers (CCBs). In animal models of obesity and diabetes, treatment with CCBs promoted restoration of insulin secretion, glycemic control, and reduction of pancreatic beta-cell apoptosis. In addition, hypertensive individuals treated with CCBs presented a lower incidence of DM when compared with other antihypertensive agents. In this review, we propose that pharmacological manipulation of the Ca2+/cAMP interaction system could lead to important targets for pharmacological improvement of insulin secretion in DM type 2.