Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM), at least in the majority of patients characterized by insulin resistance and increased visceral fat, appears to be precipitated by the exposure of tissues to excessive levels of free fatty acids; this can contribute to the muscle insulin resistance, excessive hepatic gluconeogenesis, and beta cell dysfunction that collaborate to impair glycemic control. The resultant hyperglycemia, in turn, exacerbates the insulin resistance and beta cells dysfunction. The failure of glucose-stimulated insulin secretion (GSIS) in beta cells helps to sustain the elevations of serum glucose and free fatty acids, which in turn reinforce the failure of GSIS, possibly by inhibiting expression of the transcription factor IDX-1; NIDDM thus represents a vicious cycle that is not easily broken. A new strategy for achieving rapid loss of body fat - hepatothermic therapy (HT), an integrated approach involving exercise training, low-fat, low-glycemic-index food choices, and a supplementation program that promotes hepatic fatty acid oxidation - shows promise for alleviating the excessive fat exposure at the root of the diabetic syndrome, as well as the underlying insulin resistance syndrome responsible for increased macrovascular risk. However, when HT proves incapable of breaking the vicious cycle sustaining beta cell dysfunction, a supplementary strategy, beta cell redifferentiation therapy (BRT), may be required. BRT consists of a protocol in which near-normoglycemia is maintained for several weeks through use of intensive insulin therapy (e.g. artificial pancreas) or other effective measures, during which time beta cell GSIS can be expected to substantially recover owing to relief from glucolipotoxicity. Clinical experience demonstrates that this improved beta cell function, in certain cases, can persist for months or years after temporary BRT. A portion of the improved glycemic control achieved with very low calorie diets in NIDDM is reflective of improved GSIS, presumably consequent to a sustained reduction in diurnal glycemia. Long-lived analogs of glucagon-like peptide-1 (GLP-1) may find a key role in BRT; this incretin hormone not only potentiates GSIS, but also appears to increase the expression and activity of IDX-1 in beta cells, thus promoting beta cell redifferentiation. If HT is instituted prior to and following BRT to alleviate the FFA overexposure that initially precipitated the diabetic syndrome, it seems likely that the benefits of BRT will be conserved in the long term, thus enabling a reversal of NIDDM - in other words, maintenance of normoglycemia without medication. Since NIDDM is inherently preventable, its reversal should be the fundamental goal of diabetes therapy.
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PMID:Incorporation of beta cell redifferentiation therapy into a lipoprivic strategy for reversing type 2 diabetes. 1232 11

Plasma levels of glucose, insulin and glucagon were measured at various time intervals after pancreatic duct ligation (PDL) in rabbits. Two hyperglycemic periods were observed: one between 15-90 days (peak at 30 days of 15.1 +/- 1.2 mmol/l, p < 0.01), and the other at 450 days (11.2 +/- 0.5 mmol/l, p < 0.02). The first hyperglycemic episode was significantly correlated with both hypoinsulinemia (41.8 +/- 8 pmol/l, r = -0.94, p < 0.01) and hyperglucagonemia (232 +/- 21 ng/l, r = 0.95, p < 0.01). However, the late hyperglycemic phase (450 days), which was not accompanied by hypoinsulinemia, was observed after the hyperglucagonemia (390 days) produced by abundant immunostained A-cells giving rise to a 3-fold increase in pancreatic glucagon stores. The insulin and glucagon responses to glucose loading at 180, 270 and 450 days reflected the insensitivity of B- and A-cells to glucose. The PDL rabbit model with chronic and severe glycemic disorders due to the predominant role of glucagon mimicked key features of the NIDDM syndrome secondary to exocrine disease.
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PMID:Insulin and glucagon impairments in relation with islet cells morphological modifications following long term pancreatic duct ligation in the rabbit--a model of non-insulin-dependent diabetes. 1236 13

Glucagon-like peptide-1 (GLP-1) is a 30-residue peptide implicated in short-term appetite regulation. Its analogs are presumed to be potential drugs against obesity and non-insulin dependent diabetes mellitus (NIDDM or type 2 diabetes). This study examined how the dynamic fingerprints can be used for establishing dynamics-activity relationships in a series of peptides for which the mechanism of action is unknown and in which mutations can cause an increase or decrease in biological activity. The 3D autocorrelation method was used to generate maps of both active and inactive analogs. As the active conformation of GLP-1 is not yet clearly defined, the dynamic fingerprints of peptides in an aqueous environment were compared to explain the high affinity of the peptide for its receptor. The suggestion that the peptide could bind to the receptor in a folded conformation has been examined. In the case of the GLP-1 analogs, it was shown that the folding tendency cannot be directly related to affinity values and the results do not favor a folded active conformation model of GLP-1.
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PMID:Peptide dynamic fingerprints: a tool for investigating the role of conformational flexibility for GLP-1 analogs affinity. 1564 Nov 5

This paper summarizes the new classification of diabetes mellitus (and other categories of glucose intolerance) and presents some clinically important aspects of the new insulins. The new classification promises to bring to the field considerable uniformity, previously lacking. The five clinical classes are: Type I (insulin-dependent diabetes mellitus, IDDM), Type II (non-insulin-dependent, NIDDM), "other types", gestational diabetes (GDM) and impaired glucose tolerance (IGT). The two statistical risk classes are: previous abnormality of glucose tolerance (Prev AGT) and potential abnormality of glucose tolerance (Pot AGT). These are mutually exclusive classes. Criteria recommended for use by clinicians and researchers are presented in detail, as well as information on the oral glucose test and normal glucose tolerance. Particular attention is drawn to the differences in glucose metabolism (tolerance) characteristics in non-pregnant adults, children and pregnant females. The new insulins are so called because of increased purity achieved by new purification methods. They are not new formulations or types of insulin. Contamination of insulin preparations by other hormones or compounds (e.g. glucagon, pro-insulin, pancreatic polypeptide) is now at a very low level.
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PMID:Diabetes update. 2128 88


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