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OBJECTIVE Leptin released from adipocytes plays a key role in the control of food intake, energy balance, and glucose homeostasis. In addition to its central action, leptin directly affects pancreatic beta-cells, inhibiting insulin secretion, and, thus, modulating glucose homeostasis. However, despite the importance of glucagon secretion in glucose(More)
Pancreatic α cells are exposed to metabolic stress during the evolution of type 2 diabetes (T2D), but it remains unclear whether this affects their survival. We used electron microscopy to search for markers of apoptosis and endoplasmic reticulum (ER) stress in α and β cells in islets from T2D or non-diabetic individuals. There was a significant increase in(More)
The recent discovery that genetically modified α cells can regenerate and convert into β-like cells in vivo holds great promise for diabetes research. However, to eventually translate these findings to human, it is crucial to discover compounds with similar activities. Herein, we report the identification of GABA as an inducer of α-to-β-like cell conversion(More)
Pancreatic β-cells are destroyed by an autoimmune attack in type 1 diabetes. Linkage and genome-wide association studies point to >50 loci that are associated with the disease in the human genome. Pathway analysis of candidate genes expressed in human islets identified a central role for interferon (IFN)-regulated pathways and tyrosine kinase 2 (TYK2).(More)
Leptin plays an important role in the control of food intake, energy expenditure, metabolism, and body weight. This hormone also has a key function in the regulation of glucose homeostasis. Although leptin acts through central and peripheral mechanisms to modulate glucose metabolism, the pancreatic β-cell of the endocrine pancreas is a critical target of(More)
Type 1 diabetes (T1D) is an autoimmune disease caused by loss of pancreatic β cells via apoptosis while neighboring α cells are preserved. Viral infections by coxsackieviruses (CVB) may contribute to trigger autoimmunity in T1D. Cellular permissiveness to viral infection is modulated by innate antiviral responses, which vary among different cell types. We(More)
Atrial natriuretic peptide (ANP) and its guanylyl cyclase-A (GC-A) receptor are being involved in metabolism, although their role in the endocrine pancreas is still greatly unknown. The aim of this work is to study a possible role for the ANP/GC-A system in modulating pancreatic beta-cell function. The results presented here show a direct effect of the GC-A(More)
Leptin, released by adipocytes, can modulate glucose homeostasis through direct actions on pancreatic alpha and beta cells. Although this hormone rapidly regulates alpha cell exocytosis, its long-term effects on glucagon gene expression are currently unknown. We analysed glucagon mRNA levels and protein content in alphaTC1-9 cells and isolated mouse islets(More)
Insulin resistance and hyperinsulinemia are generally associated with obesity. Obese nondiabetic individuals develop a compensatory β-cell response to adjust insulin levels to the increased demand, maintaining euglycemia. Although several studies indicate that this compensation relies on structural changes, the existence of β-cell functional adaptations is(More)
Obesity is frequently associated with insulin resistance. To compensate for this situation and maintain normoglycaemia, pancreatic beta-cells undergo several morphofunctional adaptations, which result in insulin hypersecretion and hyperinsulinaemia. However, no information exists about pancreatic alpha-cells during this compensatory stage of obesity. Here,(More)