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)

1. Neuropeptide Y is a potent appetite stimulant and has been found to modulate glucose metabolism when given chronically. The acute effects of neuropeptide on peripheral glucose handling have not been studied in detail. We have studied the acute effects of central nervous system injection of neuropeptide on glucose metabolism in vivo in the rat. 2. Rats implanted with chronic cannulae in the third cerebral ventricle were injected with either neuropeptide Y or saline and peripheral insulin sensitivity was assessed during a hyperinsulinaemic euglycaemic clamp. The effect of centrally injected neuropeptide Y on post-absorptive glucose metabolism was studied using a constant infusion of [6-3H]glucose. 3. Infusion of neuropeptide Y resulted in a 18% increase in glucose requirement during the clamp, suggesting increased peripheral tissue responsiveness to insulin. Neuropeptide Y injection in 10h fasted rats increased plasma glucose (area under curve 9.9 +/- 0.2 versus 9.1 +/- 0.1 mmol h-1l-1, P < 0.01), insulin (103 +/- 23 versus 33 +/- 8 pmol/l, P < 0.01, at 30 min) and glucagon (5.5 +/- 0.5 versus 3.1 +/- 0.3 pmol/l, P < 0.05, at 30 min). The increase in plasma glucose was due to an initial increase in the rate of appearance, which peaked between 20 and 30 min after neuropeptide Y infusion; over the entire 90 min 16% more glucose entered the systemic circulation in the neuropeptide Y-treated rats than in control rats, and the total quantity of glucose removed was also greater. 4. Neuropeptide Y in the central nervous system influences glucose metabolism by altering secretion of islet hormones, hepatic glucose production and the peripheral response to insulin.
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PMID:Acute effects of central neuropeptide Y injection on glucose metabolism in fasted rats. 854 70

Basal and postprandial concentrations of gastrointestinal hormones were measured in 12 dogs before and at one and three months after a 75% small bowel resection. Five animals were studied again at six months. Concentrations of enteric hormones and neuropeptides, measured in the proximal jejunum and distal ileum adjacent to the anastomotic site at the time of euthanasia, were compared with concentrations in control tissues taken from each animal at the time of resection. Increased basal and postprandial levels of gastrin (P < 0.05), cholecystokinin (CCK, P < 0.05), glucose-dependent insulinotropic peptide (GIP, P < 0.01), peptide YY (PYY, P < 0.001), and enteroglucagon (P < 0.001), were seen at one month after small bowel resection. In contrast, no significant changes were seen in concentrations of secretin, motilin, neurotensin, somatostatin, PP, or glucagon. Concentrations of enteroglucagon, GIP, and PYY remained high throughout the six-month study period. In contrast, gastrin and CCK had normalized by three months. Thus, only enteroglucagon, PYY, and GIP showed sustained elevations following enterectomy; the gastrin and CCK changes were transient. Following enterectomy, concentrations of vasoactive intestinal polypeptide (VIP) were reduced by about 50% in mucosal (P < 0.001) and muscle (P < 0.05) layers of proximal and distal gut. In contrast, calcitonin gene-related peptide (CGRP) was increased by about twofold in jejunal and ileal mucosa (P < 0.05), and CGRP elevations were even more marked in the muscle layers (P < 0.001). Somatostatin and neuropeptide Y (NPY) concentrations were similar to controls in all areas except for a small decrease in NPY in ileal mucosa (P < 0.05). These findings suggest that the increased motilin and PP concentrations previously reported after bowel resection in man are more likely to reflect underlying inflammatory bowel disease rather than enterectomy. The normalization of hypergastrinemia explains why the increased acid secretion after small bowel resection is transient. These results provide evidence for independent secretory control of enteroglucagon and PYY, which are both products of intestinal L cells. In addition, these studies reveal marked changes in enteric neuropeptide concentrations following bowel resection. VIP, which is thought to be a major inhibitory transmitter in the gut, is markedly reduced, while CGRP, which is mainly localized in sensory afferent fibers, is increased. These major neuropeptide changes are likely to be of importance in the adaptive responses to massive small bowel resection.
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PMID:Time course of adaptive regulatory peptide changes following massive small bowel resection in the dog. 865 52

Exhaustive characterizations of antisera to the structurally related peptides pancreatic polypeptide (PP), neuropeptide Y (NPY), and peptide YY (PYY) enabled us to establish the developmental pattern of these peptides in rat and mouse pancreas. PYY was the earliest detectable peptide and was present in all early appearing endocrine cell types. NPY appeared later and occurred exclusively in a subpopulation of insulin cells, whereas PP cells arose latest. At the earliest stage studied, all endocrine cells stored PYY. Most of these cells also contained glucagon. Subsequently, the endocrine cells comprised glucagon+PYY cells and glucagon+PYY+insulin cells. Later, cells storing either only insulin or insulin+PYY appeared. Quantitations of the relative numbers of these cell populations during development were consistent with a precursor role of triple-positive (insulin+glucagon+PYY) cells. Moreover, bromodeoxyuridine (BrdU) injections at E15.5 showed that a large percentage of triple-positive cells were in S-phase and therefore were actively dividing, whereas almost no pure insulin cells or insulin+PYY cells synthesized DNA at this time. These results suggest that PYY-positive endocrine cells may represent precursors for mature islet cells.
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PMID:PYY in developing murine islet cells: comparisons to development of islet hormones, NPY, and BrdU incorporation. 875 53

Acute administration of neuropeptide Y(NPY) into the hypothalamus and cerebral ventricles can stimulate insulin secretion in the absence of available food. However, the relationship of this effect to blood glucose and other hormones which regulate glucose metabolism remains unclear. The purpose of this study was to compare the effects of NPY injected into the third ventricle (ICV) on serum insulin, glucose, glucagon, corticosterone and non-esterified fatty acids. Studies were performed on conscious, unrestrained female rats, not given access to food. ICV NPY, 2 and 5 micrograms produced an increase in serum insulin and glucagon, while the 5 micrograms dose only increased plasma glucose transiently and increased non-esterified fatty acids for a longer period. Corticosterone was not affected by ICV NPY. The insulinaemic response to i.v. glucose, 0.5 g/kg was doubled by ICV NPY, 4 micrograms. The maximal insulin levels were 113 +/- 18 for ICV NPY versus 67 +/- 8 microU/ml for ICV saline-treated animals. The glycaemic response was not altered. The hypoglycaemic response to i.v. insulin, 0.15 U/kg was significantly attenuated by ICV NPY, 5 micrograms. We concluded that ICV NPY promotes insulin secretion in the absence of available food and may potentiate the insulinaemic response to hyperglycaemia. Furthermore, possibly through its effects on glucagon and non-esterified fatty acids, ICV NPY may decrease the ability of insulin to control glucose metabolism.
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PMID:Some acute effects of intracerebroventricular neuropeptide Y on insulin secretion and glucose metabolism in the rat. 884 19

Obesity is common and its prevalence is rising. In Singapore, a national health survey in 1992 showed that 5% of the adult population were obese and 21% were overweight. Obesity causes much morbidity and mortality and treatment is desirable. The majority of obese patients have no known cause but it is essential to exclude any underlying cause before treatment. Antiobesity drugs should be used as an adjunct to an adequate programme of dietary restriction, exercise and behavior modification. Serotonergic drugs and adrenergic agents are available in the treatment of obesity. The short-term efficacy and safety of antiobesity drugs such as fenfluramine and d-fenfluramine are proven. The long-term use of antiobesity drugs used singly or in combination remains to be established. Many peptides (cholecystokinin, glucagon, bombesin, neurotensin, etc) with weight reduction properties are undergoing extensive studies: their clinical applications are experimental. The treatment of obesity is difficult and frustrating and antiobesity drugs have an established short-term role. In morbid obesity where the life of the patient is in danger, surgery such as gastric plication may be life-saving. The recent discovery of leptin (1994) and neuropeptide Y (1995) are important breakthrough in obesity research; hopefully further research may produce more effective treatment of obesity in man.
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PMID:Current management of obesity. 894 35

To study islet function following reduced insulin sensitivity, we examined mice of the C57BL/6J strain, the genotype of which carries an increased propensity to develop insulin resistance when metabolically challenged. The mice received either a high-fat diet (58% fat on an energy basis) or a control diet (11% fat) for 12 weeks. The body weight of mice on the high-fat diet increased significantly more than that of mice on the control diet (25.8 +/- 0.4 v 21.3 +/- 0.2 g, P < .001). Already after 1 week on the high-fat diet, a significant hyperglycemia accompanied by hyperinsulinemia had evolved, indicative of insulin resistance. After 12 weeks, plasma glucose levels for high-fat diet-treated mice were 7.5 +/- 0.1 mmol/L, versus 6.5 +/- 0.1 mmol/L in controls (P < .001); corresponding values for plasma insulin were 248 +/- 17 and 104 +/- 7 pmol/L, respectively (P < .001). Mice given a high-fat diet also had elevated levels of total cholesterol, triglycerides, and free fatty acids (FFAs) compared with controls. After 4, 8, and 12 weeks, glucose (2.8, 8.3, or 16.7 mmol/kg) or the cholinergic agonist carbachol (0.16 or 0.53 micromol/kg) was injected intraperitoneally. The insulinotropic response to glucose was not different between the two groups after 4 or 8 weeks, whereas after 12 weeks, glucose-induced insulin secretion was markedly impaired in high-fat diet-treated mice (P < .001). In contrast, after 8 and 12 weeks on a high-fat diet, carbachol-stimulated insulin secretion was potentiated (P < .01), whereas carbachol-stimulated glucagon secretion was not significantly altered. Furthermore, after 12 weeks on the high-fat diet, insulin secretion from isolated islets was impaired at glucose levels of 8.3, 11.1, and 16.7 mmol/L (P < or = .05). Moreover, islet morphology as examined by immunocytochemistry using insulin antibodies and islet innervation, as revealed by immunostaining of tyrosine hydroxylase (TH), neuropeptide Y (NPY), galanin, vasoactive intestinal polypeptide (VIP), and substance P (SP) were unaffected by the high-fat diet for 12 weeks. However, quantitative in situ hybridization showed a 3.5-fold upregulation of insulin gene expression in response to the high-fat diet (P < .001) despite unaltered B-cell mass and pancreatic insulin content. We conclude that as little as 1 week of treatment with a high-fat diet induces insulin resistance in C57BL/6J mice. This is accompanied later by hyperlipemia, potentiated carbachol-stimulated insulin secretion, and increased insulin gene expression but impaired glucose-stimulated insulin secretion. We suggest that after several weeks' duration, insulin resistance is accompanied by enhanced islet sensitivity to cholinergic activation and exaggerated insulin gene expression, whereas the failing islet sensitivity to glucose represents decompensation.
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PMID:Dissociated insulinotropic sensitivity to glucose and carbachol in high-fat diet-induced insulin resistance in C57BL/6J mice. 900 77

1. Adipose tissue mass is dependent on both the average volume and the number of its constituent adipocytes. Significant alteration in body mass involves alteration in both adipocyte volume and number. 2. Increases in adipocyte number occur via replication and differentiation of preadipocytes, a process which occurs throughout life. Decreases in adipocyte number occur via preadipocyte and adipocyte apoptosis, and possibly adipocyte dedifferentiation. 3. Overall regulation of adipose mass involves endocrine, paracrine and possibly autocrine systems. Hypothalamic centres appear to control appetite, metabolic rate and activity levels in a co-ordinated manner. Within the hypothalamus, known weight regulatory molecules include glucagon-like peptide-1, neuropeptide Y and leptin. Leptin is a major afferent signal from adipose tissue to the hypothalamus, providing information on overall adipose tissue mass. However, the precise means by which the hypothalamus signals to adipose tissue is less well understood. 4. In adipose tissue, known molecular regulators of adipose cell number include insulin, ligands for the peroxisome proliferator activated receptor-gamma, retinoids, corticosteroids and tumour necrosis factor-alpha. The net effect of these and other regulators is to effect a concerted alteration in adipocyte volume and number. This review largely focuses on the control of fat cell acquisition and loss and the influence of these processes on adipose tissue mass and regional distribution.
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PMID:Regulation of adipose cell number in man. 903 86

Acute administration of neuropeptide Y(NPY) into the hypothalamus and third cerebral ventricle (ICV) increases respiratory quotient, reduces energy expenditure and increases circulating, insulin, glucagon and corticosterone. Therefore, it is likely that hypothalamic NPY has acute effects on the metabolism of fuels, such as glucose. To test this hypothesis, we determined if ICV infusion of NPY influences glucose metabolism and its sensitivity to insulin in conscious, unrestrained rats, not given access to food. Glucose turnover was 4.7+/-0.3 mg/min, 45-55 min after ICV NPY was administered at 3 microg/h vs 3.7+/-0.2 (P<0.05) for ICV saline. In a time course study, glucose turnover was significantly increased 30 min, and remained elevated at 50 min after starting a similar ICV NPY infusion. In neither study was plasma glucose, insulin, glucagon or corticosterone significantly affected by ICV NPY. During an hyperinsulinaemic euglycaemic clamp, the glucose infusion rate corrected for body weight and insulin concentration, M/I was 0.22+/-0.03 for NPY vs 0.36+/-0.05 mg min(-1) kg(-1) microU(-1) ml (P<0.05) for saline. NPY treatment prevented the decline in glucose production rate but did not influence the rise in glucose disposal rate resulting from hyperinsulinaemia. It was concluded that ICV NPY rapidly stimulates glucose turnover by a mechanism that does not depend on changes in insulin, glucagon or corticosterone secretion. Furthermore, ICV NPY decreased insulin sensitivity by reducing the effect of insulin on glucose production but not on whole body glucose disposal.
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PMID:Intracerebroventricular neuropeptide Y acutely influences glucose metabolism and insulin sensitivity in the rat. 904 62

Currently there is debate regarding the capacity of pancreatic islets to regenerate in adult animals. Because pancreatic endocrine cells are thought to arise from duct cells, we examined the pancreatic ductal epithelium of the diabetic NOD mouse for evidence of islet neogenesis. We have evidence of duct proliferation as well as ductal cell differentiation, as suggested by bromodeoxyuridine-labeling and the presence of glucagon-containing cells within these ducts. In addition, the ductal epithelia in diabetic NOD mice expressed the neuroendocrine markers neuropeptide Y and tyrosine hydroxylase. These ducts also expressed the homeobox gene product, insulin promoter factor 1. Ductal cell proliferation and expression of these markers was not observed in transgenic NOD mice (NOD-E), which do not develop clinical or histopathological symptoms of IDDM. This suggests that the observed ductal cell proliferation and differentiation was a direct result of beta-cell destruction and insulin insufficiency in these adult diabetic mice, which further suggests that these events are recapitulating islet ontogeny observed during embryogenesis. It is possible that comparable processes occur in the human diabetic pancreas.
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PMID:alpha-Cell neogenesis in an animal model of IDDM. 907 99

It has been suggested that members of the neuropeptide Y (NPY) family of regulatory peptides [NPY, peptide YY (PYY) and pancreatic polypeptide (PP)] play an important role in the development of the endocrine pancreas. The development of rat endocrine pancreas from embryonic (E) day 12 until 30 days postpartum (P) was studied with emphasis on NPY, PYY and PP and their co-existence with insulin, glucagon and somatostatin using single and double immunostaining and in situ hybridization. Already at E12, PYY was detectable in small endocrine cell clusters and found to be co-localised with both insulin and glucagon, which at this stage occurred in the same cells. At E16 most of the insulin-immunoreactive (IR) cells were distinct from the glucagon/PYY-IR cells. Interestingly, at E16 NPY mRNA, and at E17 NPY immunoreactivity appeared in a few, scattered endocrine cells. Virtually all NPY-IR endocrine cells were insulin-producing beta cells. At E18 the endocrine cells started to form typical islets with centrally located insulin/NPY-IR cells surrounded by glucagon/PYY-IR cells. AT E20-E21, the vast majority of insulin-producing cells also expressed NPY. However, at birth (day 0) islet cell NPY mRNA was lacking. Postnatally the number and immunostaining intensity of NPY-IR islet cells rapidly declined, being non-detectable at P5. Cells containing PP immunoreactivity and PP mRNA were first detected at E21. The adult pattern of islet peptide distribution, with NPY confined to neuronal elements. PYY and PP exclusively in endocrine cells, was established at P5. The beta cell expression of NPY during the latter part of embryogenesis coincides with the prepartal glucocorticoid surge and with rapid islet cell replication and differentiation. This is compatible with steroid induction of NPY expression and with a role for NPY in the maturation of beta cells and their hormone release, which occurs in the immediate neonatal period.
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PMID:Developmental expression of NPY, PYY and PP in the rat pancreas and their coexistence with islet hormones. 910 Feb 83


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