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)

Effects of insulin and glucagon on lipoprotein lipase activity in rat adipose tissue were studied in vitro. Adipose tissue from normal or streptozotocin-diabetic rats was incubated in Krebs-Ringer bicarbonate buffer for 60 min at 38 degrees C in the presence of heparin and lipoprotein lipase released from the tissue into the incubation medium was measured. Diabetic rats showed markedly low activities of adipose tissue lipoprotein lipase. Insulin (500 microU/ml) increased lipoprotein lipase activity in adipose tissue from diabetic rats. Glucagon (500 pg/ml), on the other hand, decreased the enzyme activity in normal rat adipose tissue. The results indicate that insulin and glucagon cause reciprocal changes of lipoprotein lipase activity in rat adipose tissue.
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PMID:Reciprocal changes, caused by insulin and glucagon, of adipose tissue lipoprotein lipase in rats in vitro. 701 8

Recent work in our laboratory has shown that oral administration of triphenyltin fluoride (TPTF) evokes hypertriglyceridemia in rabbits. The present experiments were conducted to elucidate the mechanism of TPTF-induced hypertriglyceridemia in rabbits by a combined biochemical and ultrastructural approach. After a single TPTF administration, fasting blood glucose and plasma triglyceride levels increased significantly (P less than 0.02) for about 20 days. On the other hand, both plasma and adipose tissue lipoprotein lipase (LPL) activity was markedly decreased (P less than 0.001) during this period, and triglyceride production rates on day 2 after TPTF administration was significantly decreased (P less than 0.01). Density-gradient ultracentrifugation showed a remarkable accumulation of chylomicron and VLDL in the composition of plasma lipoproteins. Insulin injection to the hypertriglyceridemic rabbits induced a significant recovery of the decreased plasma LPL activity with a concomitant decrease of plasma triglyceride levels, while abeyance of insulin injection resulted in a decrease of LPL activity again. A significant inhibition of insulin release in response to the loading of glucose, glucagon, or arginine was observed in the TPTF rabbits (P less than 0.02). Inhibition of glucagon release was also observed in the arginine-loading test (P less than 0.01). Electron microscopic studies showed small abnormalities in the pancreatic islets of TPTF-treated rabbits. These findings suggest that TPTF inhibits insulin release from rabbit islets, subsequently inducing diabetic lipemia due to the insulin deficiency. Furthermore, it is possible to provide a new animal model for diabetes and diabetic lipemia by administration of TPTF to rabbits.
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PMID:Triphenyltin fluoride (TPTF) as a diabetogenic agent. TPTF induces diabetic lipemia by inhibiting insulin secretion from morphologically intact rabbit B-cell. 703 Aug 27

As part of an ongoing search for diabetes susceptibility loci, we tested linkage with non-insulin-dependent diabetes mellitus (NIDDM) for 19 candidate loci or regions chosen for their potential to affect directly or indirectly the action of insulin. Loci were associated with insulin resistance, known effects on lipid metabolism, or effects on glucose metabolism or insulin action. Loci included the insulin-responsive (GLUT4) glucose transporter, hexokinase 2, glucagon, growth hormone, insulin receptor substrate 1 (IRS1), phosphoenolpyruvate carboxykinase, hepatic and muscle forms of pyruvate kinase, hepatic phosphofructokinase, the apolipoprotein B and the apolipoprotein A2 cluster, lipoprotein lipase, hepatic triglyceride lipase, the very-low-density-lipoprotein receptor, and the Pima insulin resistance locus on chromosome 4. For several candidates, no specific informative marker was available; consequently, we tested the surrounding region with highly informative markers. These regions included the diabetes-associated ras-like gene, rad, and the cholesterol ester-transfer gene, both mapped to chromosome 16. Additionally, we tested for linkage with markers at the tumor necrosis factor-alpha gene and the Friedreich's ataxia region. All regions were tested for linkage with microsatellite polymorphisms in > 450 individuals from a minimum of 16 Caucasian families under parametric (LINKAGE 5.1) and nonparametric (affected pedigree member) models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Linkage analysis of 19 candidate regions for insulin resistance in familial NIDDM. 758 21

The direct actions of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1(7-36)amide and insulin on lipoprotein lipase activity in explants of rat epididymal adipose tissues were investigated. Lipoprotein lipase was extracted into the incubation medium by heparin release of lipoprotein lipase and measured by fatty acid release from a glyceroltriolein emulsion. Insulin and glucose-dependent insulinotropic polypeptide caused a significant stimulation of lipoprotein lipase activity over a dose range of 0.25-4 nmol/L and 4-8 nmol/L, respectively. Explants incubated in the presence of both insulin and glucose-dependent insulinotropic polypeptide (at 0.5 and 4 nmol/L, respectively) showed levels of lipoprotein lipase activity significantly greater than that seen with either hormone alone. Neither insulin- nor glucose-dependent insulinotropic polypeptide-stimulated lipoprotein lipase was modified by the presence of the antibiotic actinomycin-D in the incubation medium, indicating that these two hormones exert their actions on the pre-existing cellular pool of lipoprotein lipase. Glucagon-like polypeptide-1(7-36)amide, over a dose range of 1-8 nmol/L, did not stimulate lipoprotein lipase activity. This study indicates that glucose-dependent insulinotropic polypeptide, in addition to stimulating insulin secretion, has a direct biological action on adipose tissue and in vivo, together with insulin, may promote lipoprotein lipase activity postprandially.
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PMID:Investigations into the actions of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1(7-36)amide on lipoprotein lipase activity in explants of rat adipose tissue. 786 Dec 44

The present study was undertaken to investigate fat metabolism after a high-fat meal [50 energy percent (E%) fat] in formerly obese subjects with a familial history of obesity. Twelve normal-weight postobese women (PO) and 12 closely matched controls were given the test meal after a 2-day carbohydrate-rich weight-maintenance diet (58 E% carbohydrate). Whereas the thermic effect of the meals was similar in the two groups, postprandial fat oxidation was 2.5 times more suppressed in PO compared with controls (P < 0.05). A similarly enhanced suppression of arterialized plasma concentrations of nonesterified fatty acids was seen postprandially in PO (P < 0.05), possibly due to a more marked suppression of epinephrine and a reduced glucagon response in PO than in controls. Moreover, the postprandial plasma triglyceride response was attenuated and only amounted to 43% of that in controls (P < 0.05). This may be explained by a more pronounced increase in gastric inhibitory polypeptide in PO, giving rise to a higher adipose tissue lipoprotein lipase activity. No other differences were found in plasma substrates and hormones or in subjective appetite scores. In conclusion, a metabolic and hormonal pattern favoring lipid storage was observed in postobese subjects after a high-fat meal.
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PMID:Evidence for an abnormal postprandial response to a high-fat meal in women predisposed to obesity. 794 4

Twenty-two inbred male Lewis rats were made into parabiotic pairs and 7 pairs had a further operation in which the small intestines of the 2 rats were connected so that one rat continually lost food into the upper small intestine and bloodstream of its partner. As a result, these rats showed large and sustained changes in daily food intake with one rat (A) in each pair eating more than twice as much as its partner (B) for the rest of their lives. Measurements of plasma levels of glucose, insulin, and glucagon did not vary directly with daily food intake, but integrated plasma lactate values were lower in rats that ate more (A) and higher in rats that ate less (B). At sacrifice, the rats that ate more were found to have less fat with reduced fat cell size but the same cell number in both retroperitoneal and epididymal fat pads. Measurements of the rate and pattern of glucose metabolism in retroperitoneal fat cells with or without insulin stimulation were similar across groups. Rates of lipolysis with and without epinephrine did not differ among groups. Lipoprotein lipase varied directly with fat cell size and indirectly with daily food intake. These studies show that daily food intake varies directly with fat cell size and inversely with plasma lactate and retroperitoneal lipoprotein lipase levels.
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PMID:Morphological and metabolic changes associated with large differences in daily food intake in crossed-intestines rats. 922 52

1. We investigated whether abnormalities of gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1) contribute to the hypertriglyceridaemia and hyperinsulinaemia in hypertriglyceridaemic subjects. Serum triglycerides and plasma glucose GIP, GLP-1 and immunoreactive insulin (IRI) concentrations were measured before and after a mixed meal in 15 hypertriglyceridaemic patients and in eight healthy normotriglyceridaemic control subjects. 2. Integrated post-prandial GIP concentrations were greater than in controls (P < 0.05) and correlated positively with both fasting and integrated post-prandial triglyceride concentrations (P < 0.05 for both). Fasting and integrated post-prandial IRI levels were higher in hypertriglyceridaemic subjects than in controls (P < 0.02 and P < 0.05 respectively) and correlated positively with fasting triglycerides (P < 0.02 and P < 0.001 respectively) and integrated post-prandial triglycerides (P < 0.005 and P < 0.05 respectively). There was no correlation between GIP concentrations and either fasting or post-prandial IRI levels. Fasting and post-prandial concentrations of GLP-1 were similar in patients and controls. 3. Hypertriglyceridaemic subjects have post-prandial hyperGIPaemia in addition to the well-documented hyperinsulinaemia. We found no association between GIP and insulin. There is, however, clear evidence for an association between post-prandial GIP concentrations and triglyceride levels. We suggest that this association may depend on changes in lipoprotein lipase activity and that there may be a feedback loop between GIP and triglyceride lipolysis.
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PMID:Elevated post-prandial gastric inhibitory polypeptide concentrations in hypertriglyceridaemic subjects. 940 26

In addition to its important role in maintaining glucose homeostasis, it has recently become apparent that glucose-dependent insulinotropic polypeptide (GIP) is also involved in different steps of lipid metabolism. GIP has been shown to stimulate the release of lipoprotein lipase from fat, as well as increase the rate of fat incorporation into adipose tissue. Moreover, GIP has been shown to increase the clearance rate of chylomicrons in the circulation and to inhibit the action of glucagon. Despite evidence for GIP effects on fat tissue, GIP receptors have not been identified in fat cells or tissues. The present study was undertaken to identify GIP receptors in isolated adipocytes, as well as to identify GIP receptors in the established fat cell line, differentiated 3T3-L1. RNAse protection analysis demonstrated the presence of GIP receptor transcripts in rat adipocytes. A polyclonal GIP receptor antiserum directed at the N-terminus of the receptor detected the presence of GIP receptors in both rat fat and differentiated 3T3-L1 cells by Western blot analysis. Moreover, [125I] GIP binding assays revealed both specific and displaceable GIP binding sites in differentiated 3T3-L1 cells (IC50 = 10(-9) M). When undifferentiated 3T3-L1 cells, which appear to express relatively few GIP receptors, were incubated in the presence of GIP, no effect on intracellular cAMP accumulation was detected. In contrast, the inclusion of 10 nM GIP in the incubation medium increased cAMP accumulation in rat fat cells and differentiated 3T3-L1 cells. This increase in cAMP accumulation was abolished with the specific GIP receptor antagonist GIP(7-30)NH2. The results of these studies indicate that GIP receptors are present in fat cells and are up-regulated when 3T3-L1 cells undergo differentiation to become adipocytes. Furthermore, the increase in intracellular cAMP accumulation detected upon ligand binding indicates that these receptors are functional.
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PMID:Functional GIP receptors are present on adipocytes. 972 57

In the view of lipid metabolism, adipose tissue and liver are the most important tissues for 17-beta-estradiol, the main estrogen in women's body. The lack of estrogens in women after menopause may cause coronary heart disease. It is considered, that 25 to 50% of positive effect of estrogens which are given to postmenopausal women is connected with their action on lipid metabolism. Blood plasma parameters which characterize lipid metabolism return to their physiological values during estrogens therapy. Estrogens are transferred to adipose tissue cells and liver cells by endocrine and paracrine way. They are also produced in these cells from androgens. In adipocytes 17-beta-estradiol can be stored as its esters with long-chain fatty acids. It was proved that estrogens receptors are present in adipocytes and hepatocytes but their density is much lower than in gonads. On the cellular level estrogens regulate mRNA production for particular proteins among which there are proteins involved in lipid metabolism. In adipose tissue 17-beta-estradiol has a direct effect on lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL). In the case of the first enzyme its synthesis is faster, while the synthesis of the latter is slower. On the other hand, indirect action of estrogens on adipose tissue is connected with the stimulation of the releasing of other hormones which increase HSL activity. To this group of hormones there belong catecholamines, growth hormone (GH) and glucagon. In liver 17-beta-estradiol regulates the rate of synthesis of structural apolipoproteins for VLDL and HDL. 17-beta-estradiol reduces the rate of apoB-100 synthesis, while stimulates apoA-I and apoA-II synthesis. HDL fraction containing apoA-I and apoA-II is necessary for chylomicrons and VLDL degradation as well as direct and indirect cholesterol transport to liver. Moreover, in hepatocytes estrogens stimulate the synthesis of apoC-III, while they decrease the synthesis of hepatic lipase (HL). In conclusion, 17-beta-estradiol by regulating lipid metabolism in adipocytes and hepatocytes modulates the concentration of lipid substances in plasma. The lack of 17-beta-estradiol leads likely to various lipid metabolism disorders in women after menopause. Estrogens therapy in these postmenopausal women may result in the improvement of lipid metabolism.
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PMID:[The role of estrogens in hormonal regulation of lipid metabolism in women]. 974 Nov 94

This study examines the immediate effect of modulating postprandial insulin and insulinotropic hormone (glucose-dependent insulinotropic polypeptide, GIP; glucagon-like peptide-1, GLP-1) secretion on the activation of lipoprotein lipase (LPL) in six lean and six obese age-matched women. Subjects were given, on two separate occasions, 340 kcal of carbohydrate alone or combined with an IV infusion of octreotide, (100 microg infusion from 30 min before the meal for 150 min). Post-heparin LPL activity (10,000 U) was measured on each occasion 120 minutes post-carbohydrate. Following oral carbohydrate postprandial plasma insulin levels were significantly higher in obese subjects than in lean (p < 0.01). Glucose tolerance was slightly impaired in obese subjects. Insulin, GIP and GLP-1 secretion post-carbohydrate was markedly reduced by octreotide in lean and obese subjects. LPL activity was similar in the two groups after carbohydrate administration and was unaffected by octreotide. Inhibition of postprandial insulin, GIP and GLP-1 secretion acutely did not reduce post-heparin LPL activity either in lean or obese subjects.
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PMID:Inhibition of insulin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secretion by octreotide has no effect on post-heparin plasma lipoprotein lipase activity. 1033 81


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