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)

In vivo and in vitro experiments strongly support the view that marked increases in the levels of mRNA and in the activities of lipogenic enzymes that occur in liver and white adipose tissue of the rat after weaning to a high-carbohydrate diet are dependent on an increase in plasma glucose and insulin concentrations. An increased glucose metabolism is necessary for the expression of insulin effects on fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) mRNA accumulation in white adipose tissue, as insulin is ineffective in vitro in the absence of glucose. It is suggested that intracellular glucose-6-phosphate could play an important role in the effect of insulin on lipogenic enzyme gene expression in white adipose tissue. Other hormones and substrates could also play a role in the surge of lipogenesis after weaning. The fall in plasma glucagon after weaning to a high-carbohydrate diet could reinforce the insulin-induced accumulation of FAS and ACC mRNA, as this hormone inhibits the accumulation of lipogenic enzyme mRNA in liver and white adipose tissue. The decrease in the dietary supply of fat after weaning to a high-carbohydrate diet could also potentiate the accumulation of FAS and ACC mRNA in liver because long-chain poly-unsaturated fatty acids are potent inhibitors of the expression of the genes encoding liver lipogenic enzymes. A direct effect of fatty acids on a cis-acting element of the lipogenic enzyme genes could be involved, as the regulatory region of FAS gene contains a polyunsaturated fatty acid response element that shares some similarity with the peroxisome proliferator-activated receptor recently described.
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PMID:Regulation of lipogenic enzyme gene expression by nutrients and hormones. 790 48

In cultured adipose tissue of suckling rats, glucose alone is able to induce the appearance of fatty-acid synthase and acetyl-CoA carboxylase mRNA by a mechanism involving glucose-6-phosphate accumulation; insulin alone has no effect but potentiates the effect of glucose. In the present study, we have analysed in cultured adipose tissue the effects of other hormones on the expression of these enzymes as well as on phosphoenolpyruvate carboxykinase. Triiodothyronine has only a marginal effect on fatty-acid synthase expression, in the absence or presence of glucose and insulin. A synthetic glucocorticoid, dexamethasone, opposes the inductive effect of glucose and insulin on fatty-acid synthase expression but increases the expression of phosphoenolpyruvate carboxykinase. A beta-agonist, isoproterenol totally inhibits the inductive effect of glucose and insulin on acetyl-CoA carboxylase and fatty-acid synthase expression whereas it increases the expression of phosphoenolpyruvate carboxykinase. Similarly, glucagon and cAMP have antagonistic effects on glucose and insulin-induced fatty-acid synthase expression. These inhibitory effects cannot be explained only by a reduction in glucose-6-phosphate concentration. We conclude that, in adipose tissue, dexamethasone and cAMP-generating hormones are negative regulators of lipogenic enzyme expression. Finally, the regulation of phosphoenolpyruvate carboxykinase expression in adipose tissue is similar to that found in the liver, i.e. inhibition by insulin and glucose and activation by glucocorticoids and cAMP.
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PMID:Regulation of lipogenic enzyme and phosphoenolpyruvate carboxykinase gene expression in cultured white adipose tissue. Glucose and insulin effects are antagonized by cAMP. 791 89

Fatty acid oxidation rapidly increases in the rabbit heart following birth. By inhibiting carnitine palmitoyltransferase 1 (CPT1), malonyl-CoA is a potent regulator of fatty acid oxidation in the heart. We therefore addressed the hypothesis that a decrease in acetyl-CoA carboxylase (ACC) activity and/or malonyl-CoA inhibition of CPT1 could account for the increase in the ability of the heart to oxidize fatty acids following birth. ACC activity and expression, malonyl-CoA levels, and mitochondrial CPT1 activity were measured in hearts from 1-day, 7-day, and 6-week-old rabbits. CPT1 activity and sensitivity to malonyl-CoA inhibition did not differ between 1-day, 7-day, or 6-week hearts (the IC50 for malonyl-CoA was 32.0 +/- 1.5, 36.0 +/- 0.3, and 36.3 nM, respectively). Western blot analysis with streptavidin showed that all hearts expressed similar amounts of both a 265-kDa (ACC-265) and 280-kDa isoform (ACC-280) of ACC. A progressive and significant decrease in malonyl-CoA levels was seen in 1-day, 7-day, and 6-week hearts (47 +/- 2, 40 +/- 2, and 26 +/- 2 nmol/g dry weight, respectively), paralleling a decline in ACC activity. We hypothesized that these developmental changes could be due to changes in hormonal regulation of cardiac ACC in the postnatal period. In isolated hearts from 1-day-old rabbits, the fatty acid oxidation rate was 9.01 +/- 1.10 nmol.g dry weight-1.min-1. Glucagon (1 ng/ml) did not alter this rate (11.03 +/- 1.42 nmol.g dry weight-1.min-1), but insulin (100 microunits/ml) resulted in a significant decrease in rate (4.81 +/- 0.82 nmol.g dry weight-1.min-1). ACC activity was markedly elevated in 1-day-old hearts perfused with insulin compared to control hearts or glucagon perfused hearts (0.415 +/- 0.052, 0.095 +/- 0.018, and 0.133 +/- 0.013 nmol of malonyl-CoA produced.g dry weight-1.min-1, respectively). Malonyl-CoA levels were also markedly elevated in 1-day hearts perfused with insulin (123.0 +/- 8.3, 2.0 +/- 0.4, and 1.8 +/- 0.6 nmol/g dry weight in insulin, control, and glucagon hearts, respectively). In 7-day-old rabbit hearts, the basal fatty acid oxidation rate had increased to 24.5 +/- 4.8 nmol.mg-1.min-1. In contrast to the 1-day-old hearts, insulin had no significant effect on fatty acid oxidation, although glucagon resulted in a significant increase in rates (38.9 +/- 12.2 and 80.7 +/- 9.1 nmol.g dry weight-1.min-1, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acetyl-CoA carboxylase involvement in the rapid maturation of fatty acid oxidation in the newborn rabbit heart. 792 91

The mechanisms by which triiodothyronine (T3), glucose, insulin, and glucagon regulate acetyl-CoA carboxylase expression in primary cultures of chick embryo hepatocytes have been investigated. Incubating hepatocytes with T3 in the absence of glucose caused a fourfold increase in acetyl-CoA carboxylase activity. Addition of glucose (20 mM) enhanced the T3-induced increase in acetyl-CoA carboxylase activity by threefold but had no effect on enzyme activity in the absence of T3. The effects of T3 and glucose on acetyl-CoA carboxylase activity were accompanied by similar changes in acetyl-CoA carboxylase mRNA levels, indicating that regulation occurred at a pretranslational step. Xylitol mimicked the effect of glucose on acetyl-CoA carboxylase mRNA abundance, suggesting that an intermediate(s) of the nonoxidative branch of the pentose phosphate pathway may be involved in mediating this response. Insulin accelerated the accumulation of acetyl-CoA carboxylase mRNA abundance caused by T3 and glucose but had no effect on steady-state levels of acetyl-CoA carboxylase mRNA in the absence or presence of T3. Glucagon caused a 65% decrease in the accumulation of acetyl-CoA carboxylase mRNA in hepatocytes incubated with T3 and glucose. The effects of T3, glucose, insulin, and glucagon on the abundance of acetyl-CoA carboxylase mRNA were accounted for by changes in the transcription rate of the acetyl-CoA carboxylase gene. These data support the hypothesis that T3, glucose, insulin, and glucagon play a role in mediating the effects of nutritional manipulation on transcription of acetyl-CoA carboxylase in liver.
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PMID:Triiodothyronine stimulates and glucagon inhibits transcription of the acetyl-CoA carboxylase gene in chick embryo hepatocytes: glucose and insulin amplify the effect of triiodothyronine. 901 9

Avian lipogenesis was studied in the chicken hepatocarcinoma LMH cell line. The differentiated and lipogenic status of these cells was evidenced by the presence of the albumin mRNA as well as of some mRNA coding for enzymes involved in lipogenesis (acetyl-CoA carboxylase, fatty acid synthase, delta 9 desaturase) and for apoproteins (apoprotein B and A1). These results were further confirmed by the analysis of triglyceride synthesis and secretion rates in growing cells. A time course analysis showed that triglyceride metabolism was affected by cell density. Hormone responsiveness of triglyceride production was also analyzed. Insulin, triiodothyronine and glucagon to a lesser extent were shown to regulate lipogenesis of LMH cells. The results were compared with those obtained in primary cultures of chicken hepatocytes.
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PMID:Triglyceride synthesis and secretion and lipogenesis implicated gene expression in the chicken hepatocarcinoma cell line LMH. 940 72

The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of L-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin.
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PMID:ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. 1020 99

Epidemiological studies have suggested that repeated weight cycling over time may increase the risk of coronary heart disease. The mechanism involved remains poorly understood, but the change in lipid metabolism during weight cycling has been offered as a possible explanation. The present study investigated the effect of weight cycling on the size and fatty acid composition of rat fat pads as well as serum cholesterol, triglyceride, glucose, insulin, and glucagon in rats. Two consecutive weight cycles were induced by 40% energy restriction followed by ad libitum refeeding of either a moderate-fat (MF; 22% energy) or a high-fat (HF; 45% energy) diet. The lipogenic enzymes, including fatty acid synthase, acetyl-CoA carboxylase, malic enzyme, pyruvate kinase, and lipoprotein lipase in the weight-cycled (WC) rats fed only the HF diet, yielded an overshoot of activities at the end of two weight cycles. These changes were accompanied by an 80% increase in the size of the adipocyte and a 40-50% increase in the size of perirenal and epididymal fat tissues in HF-WC rats. Regardless of whether the rats were fed the HF or MF diet, all WC rats showed a gradual reduction in linoleic and alpha-linolenic acid and an increase in palmitic, palmitoleic, and stearic acid in total body lipid. It is concluded that weight cycling in rats may promote body fatness if an HF diet is consumed and can significantly alter whole body fatty acid balance irrespective of whether they consumed an MF or HF diet. Most importantly, the weight cycling led to an overshoot or fluctuation of serum cholesterol, triglyceride, glucose, insulin, and glucagon. If weight cycling is associated with an increased risk of cardiovascular disease, then, part of the mechanism may involve the changes in these risk factors.
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PMID:Weight cycling-induced alteration in fatty acid metabolism. 1095 77

Several nondigestible but fermentable dietary carbohydrates are able to regulate lipemia and triglyceridemia in both humans and animals. The mechanism of their serum lipid-lowering effect remains to be elucidated. Oligofructose, which is a mixture of nondigestible and fermentable fructans, can decrease triacylglycerol in VLDL when given to rats. The triacylglycerol-lowering action of oligofructose is due to a reduction of de novo fatty acid synthesis in the liver through inhibition of all lipogenic enzymes, namely acetyl-CoA carboxylase (EC 6.4.1.2), fatty acid synthase, malic enzyme (EC 1.1.1.40), ATP citrate lyase (EC 4.1.3.8), and glucose-6-phosphate dehydrogenase (EC 1.1.1.49). Our results suggest that oligofructose decreases lipogenic enzyme gene expression. Postprandial insulin and glucose concentrations are low in the serum of oligofructose-fed animals and this could explain, at least partially, the metabolic effect of oligofructose. Moreover, some events occurring in the gastrointestinal tract after oligofructose feeding could be involved in the antilipogenic effect of this fructan: the production of propionate through fermentation, a modulation of the intestinal production of incretins (namely glucose-dependent insulinotropic peptide and glucagon-like peptide-1), or the modification of the availability of digestible carbohydrates. Recent studies showed that the hypotriglyceridemic effect of fructans also occurs in humans.
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PMID:Effects of fructans-type prebiotics on lipid metabolism. 1115 57

Liver X receptors (LXRs) alpha and beta, transcription factors of a nuclear hormone receptor family, are expressed in pancreatic islets as well as glucagon-secreting and insulin-secreting cell lines. Culture of pancreatic islets or insulin-secreting MIN6 cells with a LXR specific agonist T0901317 caused an increase in glucose-dependent insulin secretion and islet insulin content. The stimulatory effect of T0901317 on insulin secretion was observed only after >72 h of islet culture with the compound. In MIN6 cells, T0901317 increased protein expression of lipogenic enzymes, fatty acid synthase, and acetyl-CoA carboxylase. LXR activation also produced an increase in glucokinase protein and pyruvate carboxylase (PC) activity levels. The PC inhibitor phenylacetic acid abolished the increase in insulin secretion in cells treated with T0901317. The results suggest that LXRs can control insulin secretion and biosynthesis via regulation of glucose and lipid metabolism in pancreatic beta-cells.
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PMID:Liver X receptor activation stimulates insulin secretion via modulation of glucose and lipid metabolism in pancreatic beta-cells. 1556 26

This study aimed to test whether stimulation of net hepatic glucose output (NHGO) by increased concentrations of the AMP analog, 5-aminoimidazole-4-carboxamide-1-beta-d-ribosyl-5-monophosphate, can be suppressed by pharmacological insulin levels. Dogs had sampling (artery, portal vein, hepatic vein) and infusion (vena cava, portal vein) catheters and flow probes (hepatic artery, portal vein) implanted >16 days before study. Protocols consisted of equilibration (-130 to -30 min), basal (-30 to 0 min), and hyperinsulinemic-euglycemic (0-150 min) periods. At time (t) = 0 min, somatostatin was infused, and basal glucagon was replaced via the portal vein. Insulin was infused in the portal vein at either 2 (INS2) or 5 (INS5) mU.kg(-1).min(-1). At t = 60 min, 1 mg.kg(-1).min(-1) portal venous 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion was initiated. Arterial insulin rose approximately 9- and approximately 27-fold in INS2 and INS5, respectively. Glucagon, catecholamines, and cortisol did not change throughout the study. NHGO was completely suppressed before t = 60 min. Intraportal AICAR stimulated NHGO by 1.9 +/- 0.5 and 2.0 +/- 0.5 mg.kg(-1).min(-1) in INS2 and INS5, respectively. AICAR stimulated tracer-determined endogenous glucose production similarly in both groups. Intraportal AICAR infusion significantly increased hepatic acetyl-CoA carboxylase (ACC, Ser(79)) phosphorylation in INS2. Hepatic ACC (Ser(79)) phosphorylation, however, was not increased in INS5. Thus intraportal AICAR infusion renders hepatic glucose output insensitive to pharmacological insulin. The effectiveness of AICAR in countering the suppressive effect of pharmacological insulin on NHGO occurs even though AICAR-stimulated ACC phosphorylation is completely blocked.
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PMID:5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside renders glucose output by the liver of the dog insensitive to a pharmacological increment in insulin. 1604 57


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