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)

An end-to-side portacaval shunt was performed in a patient with severe coronary arteriosclerosis and type IIa hypercholesterolemia. By one year postoperatively there was a decrease of serum cholesterol concentration of more than 40%. No adverse side effects were noted. Intravenous and oral glucose tolerance tests were performed and were within normal range preoperatively and postoperatively. However, preoperatively, during the oral test, the serum insulin levels exceeded the normal range. In addition, glucagon levels revealed less tendency to suppression during the preoperative oral tests. Psychological testing revealed no abnormalitites, and serum ammonia levels were only slightly elevated.
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PMID:Portacaval diversion for severe hypercholesterolemia. Report of a case with measurements of glucose tolerance, insulin, and glucagon levels. 85 65

Human growth hormone (HGH) response to i.v. insulin (0.1 U/kg body weight) and arginine infusion (25 g of L-arginine for 30 min) was studied in 9 patients (5 males and 4 females) with primary familial hypercholesterolaemia and belonging to 4 families. Mean age was 28 +/- 2 years (range 18-36) and body weight was less than 105% of ideal body weight. Glucose tolerance and insulin response to oral glucose were normal in all patients. HGH release after insulin and after arginine was slightly increased as compared to 21 normal controls, but the differences were not significant. Insulin and glucagon response to arginine in these patients was within the normal range. Plasma glucose and free fatty acids were normal after both insulin and arginine. Moreover, no significant correlation was found between fasting cholesterol and HGH peaks after insulin and after arginine, nor between cholesterol and insulin and glucagon responses. Despite marked hyperlipidaemia, HGH-deficient patients examined by other authors never present signs of atherosclerotic disease. Our data suggest that HGH, in the presence of elevated cholesterol levels, might play an important role in the development of atherosclerotic lesions.
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PMID:Growth hormone response to insulin and to arginine in patients with familial hypercholesterolaemia. 120 Nov 52

Contrary to normal rats, diabetic rats are known to develop marked hypercholesterolemia when fed a cholesterol-enriched diet. The triggering factor involved in this hyperresponse has not been identified. With the aim of clarifying the role of the intestinal acyl-CoA:cholesterol acyltransferase (ACAT), we studied the effects of a high fat diet and the changes of intestinal ACAT activity during the early development of streptozotocin-diabetes in rats. Feeding diabetic rats with a diet enriched in cholesterol and saturated fat produced an increase in plasma and in tissue cholesterol as early as 3 days after streptozotocin injection in the absence of hyperphagia. Under these experimental conditions, treatment with insulin or with the ACAT inhibitor CL-277082 significantly reduced the plasma cholesterol to levels measured in nondiabetic rats fed the same high fat diet. An increase in [14C]cholesterol in plasma very low density lipoprotein was observed after oral administration of labeled cholesterol to 3-day diabetic rats. In parallel experiments, the direct measurement of small intestine microsomal ACAT activity revealed an increase, averaging 288% in diabetic rats 3 days after diabetes induction. This change in ACAT activity occurred simultaneously with an increase in plasma glucagon and was normalized by insulin treatment. The induction of intestinal ACAT activity in diabetic rats, its modulation by insulin, and the hypocholesterolemic effects of insulin or CL-277082 treatment clearly indicate that ACAT activity plays a major role in the initiation of diabetes-associated hypercholesterolemia.
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PMID:Role of the intestinal acyl-CoA:cholesterol acyltransferase activity in the hyperresponse of diabetic rats to dietary cholesterol. 143 72

Doxazosin, a selective inhibitor of alpha 1-adrenergic receptors, when administered alone or in combination with insulin or glucagon to mature ob/ob mice, consistently lowered levels of triglycerides, cholesterol, glycerol, and lactate and increased levels of beta-hydroxybutyrate and glucose. Doxazosin suppressed the tendency of insulin to elevate triglycerides but had no effect on the hypoglycemic response to insulin. Doxazosin and insulin together (but neither alone) lowered free fatty acids (FFA). Glucagon lowered cholesterol and raised glucose but did not affect triglycerides or beta-hydroxybutyrate. Analysis of variance indicates that a simple additive-effects model cannot explain the interactions between doxazosin and insulin on triglycerides, glucose, and FFA. It is suggested that the alpha 1-adrenergic system may contribute to glycemic control and to ambient hypercholesterolemia, especially in the presence of insulin resistance, as in ob/ob mice, and that the hypolipidemic response to alpha 1-adrenergic inhibition may involve insulin pathways.
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PMID:Interactions of doxazosin with insulin or glucagon in the ob/ob mouse. 247 Oct 11

Hypertriglyceridaemia is often observed in patients (1) with chronic renal insufficiency, (2) on haemodialysis and (3) after successful renal transplantation. HDL cholesterol is reduced in all three groups of patients and plasma cholesterol is elevated after renal transplantation. In these three patient groups type IV hyperlipoproteinaemia is found most frequently and after renal transplantation there is a relative increase in the incidence of type II hyperlipoproteinaemia. The role of glucagon resistance and carnitine deficiency in the alteration of fat metabolism seen in patients with chronic renal failure and patients on haemodialysis is discussed. Other factors which may influence fat metabolism in uraemia include calcium and vitamin D status as well as beta adrenergic receptor blocking agents and diuretics. Steroid therapy may be one cause of the hypercholesterolaemia and hypertriglyceridaemia seen after renal transplantation. PHLP lipase activity is reduced in all three groups of patients. In nephrotic syndrome, if hypercholesterolaemia occurs, the HDL cholesterol fraction is increased and thus the cardiovascular risk may be lower than in the three patient group mentioned above.
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PMID:[Alterations of fat metabolism in renal disease - pathogenetic mechanisms (author's transl)]. 612 54

A method was devised which increases the cholesterol concentration of rat liver plasma membranes by exchange from cholesterol-rich liposomes at low temperature (4 degrees C). When the cholesterol concentration of liver plasma membranes is increased, there is an increase in lipid order as detected by a decrease in mobility of an incorporated fatty acid spin probe. This is accompanied by an inhibition of adenylate cyclase activity. The various ligand-stimulated adenylate cyclase activities exhibit different sensitivities to inhibition by cholesterol, with inhibition of glucagon-stimulated greater than fluoride-stimulated greater than basal activity. The bilayer-fluidizing agent benzyl alcohol is able to reverse the inhibitory effect of cholesterol on adenylate cyclase activity in full. The thermostability of fluoride-stimulated cyclase is increased in the cholesterol-rich membranes. Elevated cholesterol concentrations abolish the lipid-phase separation occurring at 28 degrees C in native membranes as detected by an incorporated fatty acid spin probe. This causes Arrhenius plots of glucagon-stimulated adenylate cyclase activity to become linear, rather than exhibiting a break at 28 degrees C. It is suggested that the cholesterol contents of both halves of the bilayer are increased by the method used and that inhibition of adenylate cyclase ensues, owing to the increase in lipid order and promotion of protein-protein and specific cholesterol-phospholipid interactions.
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PMID:Elevated membrane cholesterol concentrations inhibit glucagon-stimulated adenylate cyclase. 630 41

Male adult obese (fa/fa) Zucker rats with high hypertriglyceridemia and hyperinsulinemia, and mild hypercholesterolemia were submitted to a portacaval shunt in order to examine the effects of this shunt on blood lipids and lipid synthesis. Sham-operated pair-fed obese (fa/fa) Zucker rats, obese (fa/fa) Zucker rats fed ad libitum, and lean (Fa/?) littermates fed ad libitum served as controls. In fa/fa rats 3 wk after portacaval shunt, fasting serum values of triacylglycerol (-70%) and cholesterol (-43%) were lower and plasma total glucagon was higher (+68%) than in pair-fed sham-operated fa/fa controls. In the same rats 4 wk after portacaval shunt and while fed ad libitum, serum protein was reduced by 22%, plasma pancreatic glucagon was 100% higher, and the hyperinsulinema was not modified. At that time, the wet weight of the liver and its total content in DNA, RNA, protein, and glycogen was decreased by 43%, 22%, 34%, 39%, and 60%, respectively. The in vivo incorporation of 3H2O into liver fatty acids was 76% lower and that into liver cholesterol eas 43% lower, per total organ, while the labeling of glyceride fatty acids was not modified in epididymal adipose tissue when compared with pair-fed fa/fa Zucker rats. In conclusion, portacaval shunting lowered blood triacylglycerol and cholesterol levels in fa/fa rats, and this was due, at least partially, to reduction in hepatic lipogenesis and cholesterologenesis.
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PMID:Effects of portacaval shunt on the genetically obese Zucker Rat. 728 72

Eighteen patients with non-insulin-dependent diabetes mellitus (NIDDM), who were newly diagnosed or had their oral hypoglycemic agents discontinued for more than 3 months, were studied to evaluate the effect of gliclazide on glycemic control, plasma lipids and beta cell function. The mean fasting plasma glucose (249 +/- 11 vs 170 +/- 10 mg/dl, p < 0.001), postprandial plasma glucose (353 +/- 16 vs 237 +/- 16 mg/dl, p < 0.001) and HbA1C (9.6 +/- 0.4 vs 6.5 +/- 0.3% p < 0.001) decreased significantly after 3-months of gliclazide treatment. The beta cell function showed a significant increase in fasting serum C-peptide (1.8 +/- 0.2 vs 2.1 +/- 0.3 ng/ml, p < 0.05) and an insignificant increment in serum C-peptide after glucagon stimulation (2.2 +/- 0.3 vs 2.2 +/- 0.4 ng/ml, p < 0.1). In 8 cases with an initial serum cholesterol above 200 mg/dl, the serum cholesterol decreased significantly (236 +/- 8 vs 200 +/- 12 mg/dl, p < 0.05). However, LDL-cholesterol (164 +/- 8 vs 145 +/- 13 mg, p > 0.05) and HDL-cholesterol (66 +/- 5 vs 54 +/- 9 mg, p > 0.05) showed insignificant decrease after gliclazide therapy. In 4 patients with hypertriglyceridemia, the serum triglyceride decreased (441 +/- 161 vs 239 +/- 73 mg/dl, p > 0.1), but this was not statistically significant. These findings suggest that hyperglycemia, fasting serum C-peptide levels and hypercholesteremia are significantly improved after a 3-month period of gliclazide therapy in NIDDM patients.
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PMID:Effect of gliclazide on plasma lipids and pancreatic beta cell function in non-insulin-dependent diabetes mellitus. 831 8

In order to evaluate clinical presentation and to determinate classification criteria of type 1 diabetes in the elderly, we carried out a study in 258 diabetic patients more than 60 years old of which 100 used insulin by failure to oral hypoglycemic agents (OHA). The prevalence of ischemic cardiovascular disease was 36%, peripheral vascular disease 34% and stroke 30%. Non-proliferative retinopathy 47%, nephropathy 16% and peripheral neuropathy 37%. Cardiovascular risk factors as obesity (36%), hypertension (33%) and hypercholesterolemia (12%) were evaluated. The average duration of diabetes was 20 years. Post-glucagon C-Peptide, HLA-DR antigens and islet cell antibodies (ICA), were measured in 75 older diabetic patients on treatment of which 24 used insulin, 11 diet and 40 OHA. Older patients on treatment with insulin had longer duration of disease, less obesity, low level basal of C-Peptide and a low response to post glucagon C-Peptide (0.94 +/- 0.5 pmol/ml) compared with patients on diet (1.8 +/- 0.9 pmol/ml) and OHA (1.8 +/- 0.8 pmol/ml). Older diabetics on insulin therapy had a greater frequency of HLA-DR3 (42%) and HLA-DR4 (21%) than other older diabetics. The ICA was negative in most patients. This study shows the high prevalence of macrovascular and microvascular disease in elderly patients with diabetes mellitus and that the most reliable parameter in classifying type 1 (insulin-dependent) diabetes is the measurement of basal and post-glucagon C-Peptide. HLA-DR specific markers can be used with this parameter because their expression is partly shared. This approach appears useful in the older diabetic patients to help classify diabetes and its management.
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PMID:[Diabetes mellitus in the elderly: a study on its clinical presentation, C-peptide reserve, and immunogenetic markers of insulin dependence]. 848 59

L-Arginine (Arg) is the substrate for the synthesis of nitric oxide (NO), the endothelium-derived relaxing factor essential for regulating vascular tone and hemodynamics. NO stimulates angiogenesis, but inhibits endothelin-1 release, leukocyte adhesion, platelet aggregation, superoxide generation, the expression of vascular cell adhesion molecules and monocyte chemotactic peptides, and smooth muscle cell proliferation. Arg exerts its vascular actions also through NO-independent effects, including membrane depolarization, syntheses of creatine, proline and polyamines, secretion of insulin, growth hormone, glucagon and prolactin, plasmin generation and fibrinogenolysis, superoxide scavenging and inhibition of leukocyte adhesion to nonendothelial matrix. Compelling evidence shows that enteral or parenteral administration of Arg reverses endothelial dysfunction associated with major cardiovascular risk factors (hypercholesterolemia, smoking, hypertension, diabetes, obesity/insulin resistance and aging) and ameliorates many common cardiovascular disorders (coronary and peripheral arterial disease, ischemia/reperfusion injury, and heart failure). Dietary Arg supplementation may represent a potentially novel nutritional strategy for preventing and treating cardiovascular disease.
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PMID:Arginine nutrition and cardiovascular function. 1105 97


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