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Clinical Gems

Our clinical gems come from the top selling medical books, and text books because knowledge is everything when it comes to diabetes.

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #43: Neuropeptides and Islet Hormone Secretion Part 2 of 5

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Vasoactive intestinal polypeptide (VIP): VIP was originally isolated from the porcine small intestine in the early 1970s and found to consist of 28 amino acid residues, with a C-terminal α-amidation showing structural similarities to other members of the glucagon superfamily of peptides [18]. VIP is formed by processing of 149-amino acid proVIP and is highly conserved as illustrated by human, porcine, and rat VIP increased glucose tolerance with a reduction of circulating glucose.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #42: Neuropeptides and Islet Hormone Secretion Part 1 of 5

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The traditional view is that islet hormone secretion is mainly regulated by circulating nutrients (glucose, amino acids, free fatty acids) as well as the gut incretin hormones (glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)). However, in certain circumstances regulation of insulin and glucagon secretion is also dependent on the autonomic nerves which innervate the islets. These nerves belong to the parasympathetic, sympathetic, and sensory branches of the autonomic nervous system.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #41: Normal Beta-cell Function Part 6 of 6

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Beta-Cell function and glucose homeostasis: Insulin secretion, together with the sensitivity to insulin of glucose-utilizing tissues, is a key player in glucose homeostasis. What is relevant for glucose homeostasis is not the absolute insulin secretion levels but insulin secretion relative to glucose, as typically assessed by the beta-cell dose-response during the physiologic condition of oral glucose ingestion. Thus, beta-cell glucose sensitivity is strongly inversely associated to mean glucose levels during a standard OGTT and explains, together with insulin sensitivity, a substantial proportion of the variability in glucose levels.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #40: Normal Beta-cell Function Part 5 of 6

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Beta-cell mass and function: beta-cell mass can be accurately evaluated only through autopsy studies. Complex in vivo tests aiming at measuring maximal secretory capacity combining different stimuli have been proposed as an alternative. However, their ability to discriminate between defects in function and mass, as well as their feasibility, is a matter of debate. As thoroughly reviewed by Robertson, the acute response to an i.v. glucose bolus in normoglycemic subjects and the acute response to an i.v. arginine bolus in hyperglycemic subjects do correlate with beta-cell mass.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #39: Normal Beta-cell Function Part 4 of 6

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Beta-Cell response to hormones and the nervous system: As already mentioned insulin is the only hormone with a blood glucose lowering effect, while many other hormones (glucagon, cortisol, adrenaline) exert a hyperglycemic action. The changes in glucose levels elicited by these hormones obviously will be detected by the beta cell, which will respond by enhancing insulin secretion. Yet, all these hormones, as well as others and the nervous system exert a coordinated direct effect on the beta cell resulting in an integrated and sophisticated control network.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #38: Normal Beta-cell Function Part 3 of 6

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Beta-Cell response to nonglucose secretagogues: Proteins and amino acids -- The insulinotropic effect of oral proteins was first described almost 50 years ago and recently confirmed. After the ingestion of a small amount of proteins (30–50 g) or a larger amount of proteins (2 g kg−1), plasma insulin was raised two- to threefold over baseline and remained persistently elevated for 90 or 240 minutes, respectively. In either case, blood glucose did not change, whereas both GLP-1 and GIP levels were raised threefold over fasting values.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #37: Normal Beta-cell Function Part 2 of 6

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Beta-Cell response to intravenous glucose: Although in normal living conditions beta cells are stimulated by hyperglycemia that follows glucose ingestion, the study of the response to intravenous glucose is of fundamental importance for understanding the physiology of beta cells. Several tests have been developed for this purpose and this section describes the most relevant and the characteristics of insulin secretion that they reveal.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #36: Normal Beta-cell Function Part 1 of 6

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Insulin is an ancient hormone; it emerged early in evolution since the most primitive forms of vertebrates (extant lamprey and hagfish) evolving from insulin-like peptide genes, which are expressed in all multicellular animals. From an evolutionary point of view insulin facilitates survival in an environment where access to nutrients is discontinuous, erratic, and difficult, requiring the function of highly specialized tissues necessary to allow movement and appropriate reactions to external stimuli (i.e., skeletal muscle and nervous system). Insulin, in the fed state is secreted to stimulate glucose and amino acids uptake allowing the build-up of depots of glycogen, proteins and lipids, which are necessary to sustain the energy requirements during successive fasting.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #35: Beta-Cell biology of insulin secretion Part 5 of 5

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Autocrine effect of insulin on insulin secretion: Rodent and human pancreatic beta cells possess the various components of the insulin signaling system, including insulin receptor, insulin-like growth factor-1 (IGF-1) receptor, insulin receptor substrates (IRS-1 and IRS-2), phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent kinase-1 (PDK1), and protein kinase B (PKB)/Akt. It has been shown that insulin binds to the insulin receptors on the surface of beta cells and induces phosphorylation of the insulin receptors and IRSs,modulating its own secretion. This effect of insulin is involved especially in the 1st phase of GIIS in mice.

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International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #34: Beta-Cell biology of insulin secretion Part 4 of 5

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Gs-protein-coupled receptor: In pancreatic beta cells, various hormones, neurotransmitters, nucleotides, and fatty acids including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), adrenaline, ATP/ADP, lysophosphatidylcholine (LPC), and oleoylethanolamide (OEA) activate their specific receptors. These receptors when coupled with Gs-protein activate adenylate cyclase and increase cAMP production. These cAMP-increasing ligands potentiate both the 1st phase and 2nd phase of GIIS.

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