[ Diabetes Type 1 ]

Autonomic mediation of glucagon secretion during hypoglycemia: implications for impaired alpha-cell responses in type 1


Intranasal glucagon is effective and noninferior to injectable intramuscular glucagon for the correction of insulin-induced hypoglycemia in adults with type 1 diabetes, according to a randomized, cross-over study. The findings were published today in the online edition of Cell Metabolism. The increases in epinephrine and norepinephrine were comparable in diabetics and normals; thus, the blunted response in plasma IRG to the stimulus of low blood sugar in diabetics cannot be explained by a generalized defect in catecholamine secretion. Insulin and glucagon were delivered using two subcutaneous infusion pumps installed on the abdominal wall. In conclusion, the association of Clonidine to a protein meal caused impaired glucose tolerance presumably due to a direct glycogenolytic effect, occurring in the liver on account of an α-2 receptor stimulation, insulin and glucagon not being involved in this phenomenon. LY2189265 retained full receptor activity in vitro and elicited insulinotropic activity in islets similar to native peptide. From these results we conclude that although in diabetes excessive glucagon levels are observed with chronic arginine stimulation, the acute phase of glucagon secretion in response to arginine is normal.

Although the study does not show evidence for linkage in this chromosomal region in our Italian cohort, we cannot a priori exclude the possibility of an allelic or genotypic association. Full text Full text is available as a scanned copy of the original print version. Finally, in the fifth section, we summarize the concepts underlying the autonomic hypothesis, the evidence for it, and the implications of the autonomic hypothesis for the treatment of type 1 diabetes.

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[ Nutrition ]

Autonomic mediation of glucagon secretion during hypoglycemia: implications for impaired alpha-cell responses in type 1


Type 2 diabetes (T2D) is characterized by elevated blood glucose levels owing to insufficient secretion and/or activity of the glucose-lowering hormone insulin. This study was designed to determine whether the glucagon hyperresponsiveness to arginine in these patients would improve by insulin infused at a high enough dose to overcome insulin resistance. Other new mechanistic pathways to treat patients with T2DM are the topic of ongoing preclinical and clinical research. Free cytosolic concentrations of ATP ([ATP](c)) or Ca(2+) ([Ca(2+)](c)) were imaged using alpha-cell-targeted firefly luciferase or a green fluorescent protein-based Ca(2+) probe (“pericam”), respectively. Islets were isolated from the pancreata of Wistar rats or deceased human organ donors. From these transcriptomes, we discovered that the ghrelin receptor is expressed exclusively by delta cells within the islet, which was confirmed by fluorescent in situ hybridization and qPCR. We also detected mRNA encoding ghrelin and its receptor in the rat pancreatic islets.

Furthermore, potential advantages and limitations of antagonizing the glucagon receptor or suppressing glucagon secretion in the treatment of type 2 diabetes are discussed with a focus on already marketed drugs and drugs in clinical development. Extracellular insulin (20 nmol/l) inhibited glucagon secretion from control and PASK-deficient alpha-TC1-9 cells. Fas was not observed in islet cells and Fas ligand was not observed in T cells in recent-onset fulminant type 1 diabetes patients in this study.

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