Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Regulation of the expression of the hepatic L-type pyruvate kinase gene by insulin and dietary fructose was studied in diabetic rats. Insulin increased the levels of putative nuclear RNA precursor species of this enzyme in parallel with that of total cellular pyruvate kinase L mRNA. These changes occurred more slowly than those induced by dietary fructose. Insulin caused a 3-fold increase in transcription of the pyruvate kinase L gene after 6 h and a 6-fold increase after 16 h. The increase caused by insulin was inhibited by glucagon, but not by adrenalectomy. Cycloheximide inhibited the induction caused by insulin, suggesting that insulin may stimulate transcription of the pyruvate kinase L gene by stimulating synthesis of some unknown protein. On the other hand, feeding fructose had no effect on transcription of the pyruvate kinase L gene. We previously showed that increases in the levels of putative nuclear RNA precursor species of the pyruvate kinase L after fructose feeding preceded changes in the levels of cytosolic pyruvate kinase L mRNA (Inoue, H., Noguchi, T., and Tanaka, T. (1984) J. Biochem. (Tokyo) 96, 1457-1462). Thus, dietary fructose may increase the levels of pyruvate kinase L mRNA by stabilizing nuclear RNA species. Glucagon inhibited the increase in pyruvate kinase L mRNA caused by dietary fructose. However, plasma levels of glucagon and thyroid hormones were not decreased in diabetic rats after fructose feeding. In addition, treatment with triiodo-L-thyronine caused no change in the pyruvate kinase L mRNA level. Furthermore, adrenalectomy did not impair enzyme induction by fructose in diabetic rats. Thus, the effect of fructose on pyruvate kinase L seems to be directly on the liver.
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PMID:Transcriptional and post-transcriptional regulation of L-type pyruvate kinase in diabetic rat liver by insulin and dietary fructose. 241 97

The splenic pancreas of 165 day old diabetic KKAy and age-matched nondiabetic C57BL/6 mice was examined by morphometry and immunocytochemistry at the light microscopic level and by radioimmunoassay to evaluate the morphology, surface area, endocrine cell composition and hormone content of the pancreatic islets. The insulin cells of the diabetic mice were severely degranulated and many of the glucagon, somatostatin and pancreatic polypeptide cells were displaced from the mantle to the core of the islet tissue where the non-insulin cells appeared to lose their continuity. The topography of some of the islets of KKAy mice was further deranged by acinar cells among the endocrine tissue. Morphometric analysis revealed that the surface area of the islets of KKAy mice was significantly expanded in comparison with that of C57BL/6 mice. The volume and numerical percents of the insulin cells were significantly increased whereas those of the glucagon and somatostatin cells were decreased in the KKAy mice. Since only the mean absolute number of insulin cells was elevated in the diabetic mice, the alteration in the relative proportions of the non-insulin cells and hypertrophy of the islets seemed to be a manifestation of insulin cell hyperplasia. Pancreatic insulin and somatostatin contents were markedly diminished in the islets of KKAy compared with those of C57BL/6 mice. These results demonstrate that the microscopic anatomy, endocrine cell populations and hormone content of the pancreatic islets are deranged in the KKAy mouse with severe hyperinsulinemia and hyperglycemia.
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PMID:Analysis of pancreatic islet cells and hormone content in the spontaneously diabetic KKAy mouse by morphometry, immunocytochemistry and radioimmunoassay. 244 17

Carbohydrate intolerance is common in patients with cirrhosis. The aim of the present study was to determine whether the beneficial metabolic effects of low glycemic index diets observed in noncirrhotic diabetics also occurred in patients with cirrhosis. Therefore, for one day, five patients with cirrhosis were fed diets in which low glycemic index foods were substituted, replacing those which produced higher blood glucose rises. Reduction in the estimated glycemic impact of the diet by approximately 30% reduced the mean incremental blood glucose level over the day by 40 +/- 5% (p less than 0.001). Measurement at breakfast of amino acid, insulin, and gastric inhibitory polypeptide profiles confirmed a reduction of similar magnitude. No change was seen in pancreatic glucagon, whereas enteroglucagon levels tended to be higher. In view of these findings and the possible long-term benefits of chronic reduction of hyperinsulinism and alteration in amino acid metabolism, this approach to dietary management of cirrhosis warrants further consideration.
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PMID:Low glycemic index foods and reduced glucose, amino acid, and endocrine responses in cirrhosis. 250 Aug 46

A new congenic strain of rat, the SHR/N-corpulent, provides a good model for noninsulin-dependent diabetes and was used in the present study. Corpulent rats as compared to their lean littermates are obese, hyperlipidemic, and severely hyperinsulinemic, and show an age-dependent loss of glucose tolerance. Mild fasting hyperglycemia is seen only in corpulent rats fed sucrose. Since dietary sucrose is more lipogenic than starch and since insulin and glucagon are involved in lipid and carbohydrate metabolism, we studied the effect of the type of dietary carbohydrate on insulin and glucagon levels and their receptors in lean and corpulent SHR/N rats. A significant phenotypic effect was observed (corpulent greater than lean) on plasma levels of triglyceride, cholesterol, and insulin. Dietary sucrose increased these parameters in corpulent rats but not in lean rats. Insulin and glucagon binding to liver plasma membranes was lower in corpulent rats than in lean; decreases were due to fewer receptors without a significant change in affinity. Thus, in corpulent rats, in addition to hyperinsulinemia, fewer glucagon receptors and their failure to be regulated by plasma glucagon levels appear to contribute to the hyperlipidemia. Furthermore, the hyperglycemia observed in sucrose-fed corpulent rats may be due to extreme resistance to insulin despite lower plasma glucagon and fewer glucagon receptors.
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PMID:Effect of dietary carbohydrates on insulin and glucagon receptors in a new model of noninsulin-dependent diabetes-SHR/N-corpulent rat. 255 55

To determine whether insulin regulation of lipolysis is abnormal in subjects with poorly controlled insulin-dependent diabetes mellitus (IDDM), free-fatty acid flux ([1-14C]palmitate) was measured under conditions ranging from complete insulin withdrawal to hyperinsulinemia. Seven nondiabetic and seven IDDM subjects were studied with the pancreatic clamp technique to control plasma insulin, growth hormone, and glucagon concentrations at the desired levels. Preliminary studies were performed to validate the experimental design. The palmitate flux response to insulin withdrawal (2.5 +/- 0.2 vs. 2.5 +/- 0.2 mumol.kg-1.min-1) and maximally antilipolytic insulin concentrations (0.17 +/- 0.02 vs. 0.23 +/- 0.03 mumol.kg-1.min-1) were not different in nondiabetic and IDDM subjects, respectively. In contrast, IDDM subjects required significantly greater plasma free-insulin concentrations to result in equivalent suppression of palmitate flux compared with nondiabetic subjects. Lipolysis was found to be very sensitive to insulin in nondiabetic humans, with half-maximal suppression occurring at plasma free-insulin concentrations of approximately 12 pM (less than 2 microU/ml). We conclude that adipose tissue lipolysis is normally exquisitely sensitive to insulin and that sensitivity, but not responsiveness to insulin, is impaired in poorly controlled IDDM.
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PMID:Insulin regulation of lipolysis in nondiabetic and IDDM subjects. 257 54

The role of the pattern of insulin secretion on hepatic glucose production (HGP) was evaluated with hyperglycemic and euglycemic clamp studies in six normal young nonobese subjects. In the hyperglycemic studies, glucose levels were raised and maintained at 98 mg/dl above basal for 150 min. Each subject responded with a biphasic pattern of immunoreactive insulin (IRI) release. HGP was completely suppressed by 20 min, coincident with the first-phase insulin release. HGP then rose steadily, surpassing the basal rate by 100 min when IRI had reached the peak levels of the first phase. By 130 min, when IRI had surpassed the peak first-phase levels, HGP began to fall. In the euglycemic studies with a square wave of hyperinsulinemia (approximately 25 microU/ml), HGP was suppressed to approximately 60% of basal and remained at that rate. We next repeated the hyperglycemic studies with somatostatin, glucagon, and insulin infusions. In these studies with a square wave of hyperinsulinemia (approximately 40 microU/ml, the level observed during the first phase IRI of the previous hyperglycemic clamps), HGP was suppressed to approximately 43% of basal rate and remained at that rate. These studies indicate insulin regulation of HGP is not only dependent on insulin level but may be strongly influenced by the pattern, over time, of insulin secretion.
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PMID:Escape of hepatic glucose production during hyperglycemic clamp. 257 38

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.
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PMID:Hypoglycemia associated with renal failure. 264 22

Many viral infections induce interferon (IFN) production and cause insulin resistance. To examine the causal relationship between IFN and insulin resistance, we injected natural human leukocyte IFN-alpha (3 x 10(6) IU, i.m.) twice overnight in eight healthy subjects and determined oral (OGT) and intravenous (IVGT) glucose tolerance and sensitivity to insulin (287 nmol or 40 mU.m-2.min-1 euglycemic insulin clamp) the following morning. IFN caused mild influenzalike symptoms and induced a rise in circulating glucose, insulin, hydrocortisone (cortisol), growth hormone, and glucagon concentrations (P less than .05-.001). In the OGT test, the area under the glucose curve was 2.6-fold greater (P less than .02), and the disappearance rate of intravenously administered glucose was reduced by 28% (P less than .05) after IFN administration. The impairment in OGT and IVGT occurred despite augmented insulin response. Insulin-stimulated glucose disposal was reduced by 22% (P less than .005), and insulin clearance increased by 18% (P less than .02) after IFN administration. When the insulin-clamp study was repeated in patients with steady-state hyperinsulinemia that was 12% higher (P less than .005) after IFN, the glucose disposal rate was still reduced by 15% (P less than .01). These data indicate that IFN 1) stimulates counterregulatory hormone secretion, 2) impairs glucose tolerance and insulin sensitivity, and 3) stimulates insulin clearance. Thus, IFN may be involved in the development of insulin resistance during viral infections.
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PMID:Effect of interferon on glucose tolerance and insulin sensitivity. 265 35

Hyper- and euglycemic clamp studies were performed in patients with noninsulin-dependent diabetes mellitus to examine the effects of exogenous insulin administration on insulin and glucagon secretion. Plasma glucose was kept at the fasting level [mean, 10.0 +/- 0.2 (+/- SE) mmol/L; hyperglycemic clamp], and graded doses of insulin (1, 3, and 10 mU/kg.min, each for 50 min) were infused. The plasma C-peptide level gradually decreased from 523 +/- 66 to 291 +/- 43 pmol/L (n = 13; P less than 0.005) by the end of the hyperglycemic clamp study. After 90 min of equilibration with euglycemia (5.4 +/- 0.1 mmol/L; euglycemic clamp), the same insulin infusion protocol caused a similar decrease in the plasma C-peptide level. With the same glucose clamp protocol, physiological hyperinsulinemia for 150 min (676 +/- 40 pmol/L), obtained by the infusion of 2 mU/kg.min insulin, caused suppression of the plasma C-peptide level from 536 +/- 119 to 273 +/- 65 pmol/L during hyperglycemia and from 268 +/- 41 to 151 +/- 23 pmol/L during euglycemia (n = 9; P less than 0.005 in each clamp). Plasma glucagon was suppressed to a similar degree in both glycemic states. These results demonstrate that 1) insulin secretion in non-insulin-dependent diabetes mellitus is suppressed by high physiological doses of exogenous insulin in both the hyper- and euglycemic states, the degree of inhibition being independent of the plasma glucose level; and 2) glucagon secretion is also inhibited by such doses of exogenous insulin.
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PMID:Insulin and glucagon secretion are suppressed equally during both hyper- and euglycemia by moderate hyperinsulinemia in patients with diabetes mellitus. 265 70

We measured plasma amino acid together with insulin, glucagon, pancreatic polypeptide (PP), and glucose concentrations after the ingestion of a protein meal in lean and obese subjects. The basal plasma amino acid levels were similar in both groups. The postprandial increase in the plasma amino acid levels in the obese subjects was only 15-50% of that in the lean subjects. The mean basal and peak postprandial plasma insulin levels were significantly higher (72 and 165 pmol/L) in the obese group than in the lean group (36 and 115 pmol/L; P less than 0.05-0.01). The postprandial rise in plasma glucagon was largely attenuated in the obese subjects, and there was no difference in plasma PP and glucose levels in the 2 groups. To further evaluate the role of circulating amino acids on pancreatic endocrine function in obese and lean subjects, an amino acid mixture consisting of 15 amino acids was infused iv. During the infusion the plasma amino acid levels were comparable in both groups. Plasma insulin rose by 36 +/- 7 (+/- SE) pmol/L (5 +/- 1 microU/mL) in the lean and 129 +/- 22 pmol/L (18 +/- 3 microU/mL) in the obese subjects, whereas plasma glucagon, PP, and glucose levels were similar in both groups. In view of the 3.6-fold greater insulin responses in the obese subjects, it is likely that circulating amino acids contribute to their hyperinsulinemia in spite of the reduced postprandial rise of amino acids in this group (50-85%). Thus, under physiological conditions amino acids have to be considered as an important regulatory component of postprandial insulin release in obese subjects.
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PMID:Circulating amino acids and pancreatic endocrine function after ingestion of a protein-rich meal in obese subjects. 265 33


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