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)

Chronic renal failure results in a variety of metabolic derangements that perturb glucose homeostasis. These may in part result from the fact that the kidney plays a prominent role in the metabolism of insulin as well as a number of other low-molecular-weight peptide hormones that affect carbohydrate metabolism. Specific abnormalities in glucose utilization that appear to be related to alterations in membrane receptors, resulting in increased glucagon sensitivity and decreased insulin action, are a newly recognized factor in intolerance to oral glucose. Glucose production and utilization are both abnormally increased in patients with chronic uremia, and these disturbances are only partially corrected by hemodialysis treatment. The mechanism(s) contributing to these changes is unclear, but seems to involve a combination of humoral and cellular factors. These include some degree of insulin resistance, probably inadequately modulated proteolytic responses to glucagon and parathyroid hormone, and a basic defect in energy production that alters intracellular concentrations of high-energy phosphate-containing nucleotides. It is unclear whether these changes in carbohydrate tolerance pose an increased risk for the premature development of cardiovascular disease in patients with renal failure, as they appear to do in the nonuremic population. The occasional patient with renal failure may develop clinical hypoglycemia when glucose utilization continues in a setting in which the hepatic capacity to produce glucose is reduced, probably as a consequence of altered substrate delivery and/or inhibition of one or more key gluconeogenic enzymes.
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PMID:Disorders of glucose metabolism in uremia. 11 52

The amino acid composition of the diet influences the postprandial levels of plasma amino acids along with the hormones insulin and glucagon in humans fed single test meals identical in composition except for protein source. Soy protein (hypocholesterolemic), vs. casein (hypercholesterolemic), contains a higher amount of arginine and glycine and induces an increase in postprandial arginine and glycine. Soy protein induces a low postprandial insulin/glucagon ratio in both hypercholesterolemic and normocholesterolemic subjects. Casein induces a high postprandial insulin/glucagon ratio among hypercholesterolemic subjects. Amino acids such as arginine and glycine are associated with a decrease, while lysine and branched-chain amino acids are associated with increased serum cholesterol levels. Our data are consistent with the hypothesis that the control of cholesterol by insulin and glucagon is regulated by dietary and plasma amino acids. From this hypothesis the insulin/glucagon ratio is proposed as an early metabolic index of the effect of dietary proteins on serum cholesterol levels, a risk factor and a common mechanism through which dietary and lifestyle factors influence cardiovascular disease.
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PMID:Plasma amino acids and the insulin/glucagon ratio as an explanation for the dietary protein modulation of atherosclerosis. 176 11

The efficacy and safety of gliclazide (Diamicron) were studied in 29 NIDDM patients (19 men and 10 women aged 25-68 years) who failed to improve with diet or with diet plus a sulfonylurea. All patients were overweight and had fasting blood glucose levels consistently above 150 mg/dl (8.24 mmol/l). After withdrawal of oral hypoglycemics where applicable, they received 40 mg Diamicron three times daily with meals. The dose was increased by 40-80 mg/day until optimum control was obtained or up to a maximum of 320 mg/day. Treatment lasted for 12 months. At the end of this period the mean fasting blood glucose level had fallen by 35% from 238 to 154 mg/dl and the mean 2-h postprandial blood glucose level had fallen by 28% from 237.7 to 195 mg/dl. The mean glycosylated hemoglobin level also fell by 30% from 10.10 to 7.02%, i.e. within the normal range. In addition, there was a 19% fall in triglyceride and a 10% fall in cholesterol levels, with no change in body weight. No changes were observed for serum insulin, C-peptide and glucagon levels, thyroid function tests, blood counts, liver and kidney function tests, uric acid, electrolytes, blood pressure or heart rate. No clinical or ECG abnormalities were observed in patients with or without cardiovascular disease. There were two presumptive hypoglycemic reactions, but these did not require treatment. Adverse effects were reported by 22 patients, including dizziness and light-headedness, diarrhea, nausea, palpitations and pruritus, but none required modification of Diamicron therapy. The results therefore show that Diamicron is safe, effective and well tolerated in suitably selected NIDDM patients.
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PMID:Evaluation of the efficacy and safety of Diamicron in non-insulin-dependent diabetic patients. 179 70

The amino acid composition of the diet influences the postprandial levels of plasma amino acids along with the hormones insulin and glucagon in humans fed single test meals identical in composition except for protein source. Soy protein (hypocholesterolemic), versus casein (hypercholesterolemic), contains a higher amount of arginine and glycine and induces an increase in postprandial arginine and glycine. Soy protein induces a low postprandial insulin/glucagon ratio in both hypercholesterolemic and normocholesterolemic subjects. Casein induces a high postprandial insulin/glucagon ration among hypercholesterolemic subjects. Amino acids such as arginine and glycine are associated with a decrease, while lysine and branched-chain amino acids are associated with increased serum cholesterol levels. Our data are consistent with the hypothesis that the control of cholesterol by insulin and glucagon is regulated by dietary and plasma amino acids. From this hypothesis the insulin/glucagon ratio is proposed as an early metabolic index of the effect of dietary proteins on serum cholesterol levels, a risk factor and a common mechanism through which dietary and lifestyle factors influence cardiovascular disease.
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PMID:Plasma amino acids and the insulin/glucagon ratio as an explanation for the dietary protein modulation of atherosclerosis. 194 85

Combination oral contraceptives (OCs) are probably not an independent risk factor for cardiovascular disease but through their metabolic actions, may partly amplify the effects of known risk factors for cardiovascular disease. This review of the literature and our own data indicate that use of high-dose, progestogen-dominant OCs induces a potentially atherogenic lipoprotein profile (high low-density lipoprotein-cholesterol:high-density lipoprotein-cholesterol ratio), mostly attributable to the antiestrogenic action of the progestogen content of these OCs. In contrast, lower-dose combination OCs with reduced amounts of progestogens and slight estrogen dominance, either monophasic or multiphasic, produce strikingly fewer adverse effects on lipoproteins. Moreover, use of low-dose, as opposed to high-dose, OCs results in almost unchanged glucose tolerance, marginally increased or unchanged insulin and glucagon responses to glucose, and probably unchanged levels and activity of peripheral insulin receptors. Further in-depth studies of low-dose OC formulations are mandatory to ascertain reduced metabolic risk of these OCs.
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PMID:Metabolic effects of oral contraceptives. 331 22

Historically, the sodium ion has been given prominence in relation to cardiovascular disease, perhaps to the exclusion of other ions. Recently, other ions, including chloride, potassium, magnesium and calcium have received increasing attention in relation to hypertension, cardiac arrhythmias, and metabolic derangements. Endocrine factors controlling these ions have also received increasing attention; they include classic hormonal actions as well as neurotransmission and paracrine hormonal actions. Studies indicate that control of the renin-angiotensin-aldosterone system resides in cytosolic calcium ion levels in the juxtaglomerular cell, as well as chloride ion and prostaglandins at the macula densa. Renin release is stimulated by hyperpolarisation of the juxtaglomerular cell induced by beta 1-agonists, parathyroid hormone, glucagon, magnesium and low cytosol calcium. Renin release is inhibited by high calcium, potassium and angiotensin II. Subsequent to renin release, hormonal regulation includes stimulation of converting enzyme activity by cortisol and prostaglandin (PGE2). Other hormonal control includes antidiuretic hormone producing dilution of extracellular electrolytes and augmented peripheral resistance. A recently identified natriuretic factor isolated from cardiac atria appears to be a potent diuretic with actions similar to that of frusemide (furosemide). Other electrolytes have received closer scrutiny. Chloride may play a dominant role in renal sodium reabsorption, responding to prostaglandin levels. Calcium has been recognised as a basic regulator of the secretion of such hormones as noradrenaline, renin, and aldosterone. As well, calcium ion changes are the means by which smooth muscle contraction is effected. Parathyroid hormone and vitamin D regulate the level of this ion in the body. In addition, a high dietary calcium intake appears to play a protective role against hypertension, while calcium channel blockers appear to reduce blood pressure. Endocrine systems play a major role in the protection against acute elevations in serum potassium by means of insulin action and adrenergic modulation of extrarenal potassium disposal. Aldosterone is recognised as the delayed regulator of potassium excretion. Magnesium levels fall in hyperaldosteronism, hyperparathyroidism, and diabetic keto-acidosis, as well as in malnutrition states. A coexisting potassium deficiency may be refractory to therapy until hypomagnesaemia is corrected. The integrated action of these hormones and electrolytes are thus of major importance in regulation of the cardiovascular system.
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PMID:Endocrine physiology of electrolyte metabolism. 638 78

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

This study was undertaken to determine whether the internal clock contributes to the hormone and metabolic responses following food, in an experiment designed to dissociate internal clock effects from other factors. Nine female subjects participated. They lived indoors for 31 days with normal time cues, including the natural light: darkness cycle. For 7 days they retired to bed from 0000 h to 0800 h. They then underwent a 26-h 'constant routine' (CR) starting at 0800 h, being seated awake in dim light with hourly 88 Kcal drinks. They then lived on an imposed 27-h day (18 h of wakefulness, 9 h allowed for sleep), for a total of 27 days. A second 26-h CR, starting at 2200 h, was completed. During each CR salivary melatonin and plasma glucose, triacylglycerol (TAG), non-essential fatty acids (NEFA), insulin, gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1) were measured hourly. Melatonin and body temperature data indicated no shift in the endogenous clock during the 27-h imposed schedule. Postprandial NEFA, GIP and GLP-1 showed no consistent effects. Glucose, TAG and insulin increased during the night in the first CR. There was a significant effect of both the endogenous clock and sleep for glucose and TAG, but not for insulin. These findings may be relevant to the known increased risk of cardiovascular disease amongst shift workers.
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PMID:Effects of the endogenous clock and sleep time on melatonin, insulin, glucose and lipid metabolism. 969 77

The frequent coexistence of hyperandrogenism and insulin resistance is well established; however, whether a cause and effect relationship exists remains to be established. In this study we tested the hypothesis that short-term androgen administered to women would induce insulin resistance. To test this hypothesis, regularly menstruating, nonobese women were studied before and during methyltestosterone administration (5 mg tid for 10-12 days) by the hyperglycemic (n=8) and euglycemic, hyperinsulinemic (n=7) clamp techniques. Short-term methyltestosterone administration had no significant effects on the fasting levels of glucose, insulin, c-peptide, glucagon, or glucose turnover. During the hyperglycemic clamp studies, the mean glucose level during the final hour was 203+/-2 and 201+/-1 mg/dL in the methyltestosterone and control studies, respectively. The insulin response to this hyperglycemic challenge was slightly but not significantly greater during methyltestosterone treatment (first phase 59+/-8 vs. 50+/-8 microU/mL in controls; second phase 74+/-9 vs. 67+/-9 microU/mL in controls; total insulin response 133+/-16 vs. 117+/-15 microU/mL in controls). In spite of this, glucose uptake was reduced from the control study value of 10.96+/-1.11 to 7.3+/-0.70 mg/kg/min by methyltestosterone (P < 0.05). The ratio of glucose uptake per unit of insulin was also significantly reduced from a control study value of 14.3+/-1.4 to 9.4+/-1.3 mg/kg/min per microU/mL x 100 during methyltestosterone administration. In the euglycemic hyperinsulinemic clamp studies, insulin was infused at rates of 0.25 and 1.0 mU/kg/min to achieve insulin levels of approximately 25 and 68 microU/mL, respectively. During low-dose insulin infusion, rates of endogenous hepatic glucose production were equivalently suppressed from basal values of 2.37+/-0.29 and 2.40+/-0.27 mg/kg/min to 0.88+/-0.25 and 0.77+/-0.26 mg/kg/min in the methyltestesterone and control studies respectively. Whole body glucose uptake during low-dose insulin infusion was minimally affected. During the high-dose insulin infusion, endogenous hepatic glucose production was nearly totally suppressed in both groups. However, whole body glucose uptake was reduced from the control value of 6.11+/-0.49 mg/kg/min to 4.93+/-0.44 mg/kg/min during methyltestosterone administration (P < 0.05). Our data demonstrate that androgen excess leads to the development of insulin resistance during both hyperglycemic and euglycemic hyperinsulinemia. These findings provide direct evidence for a relationship between hyperandrogenemia and insulin resistance, and its associated risk factors for cardiovascular disease.
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PMID:Effects of methyltestosterone on insulin secretion and sensitivity in women. 985 88

In the majority of patients suffering from chronic pancreatitis an endocrine pancreatic insufficiency is correlated with exocrine dysfunction. The prevalence of impaired or diabetic glucose tolerance is 40-70%, half of these patients suffer from an insulin-dependent diabetes mellitus. In general the probability of endocrine insufficiency progressively increases within the ten years following diagnosis of chronic pancreatitis. Onset and severity of the endocrine dysfunction depend on parenchymal destruction of the pancreas but are also influenced by ongoing alcohol consumption. Pathological findings in the endocrine pancreas are a loss of B-cells with decrease in secretion of insulin but also a loss of B-cell responsiveness to glucose by impaired perisinusoidal diffusion. Disturbances of the enteroinsulinar axis with diminished levels of incretins due to an exocrine insufficiency are also discussed. In addition, an impaired A-cell function may be important, that is characterized by diminished levels of stimulated glucagon. Increased plasma levels of somatostatin were found, the source of which is unknown. The susceptibility to severe hypoglycemia in patients with diabetes mellitus secondary to chronic pancreatitis is higher than in Type I diabetics. This is mainly caused by the impaired glucagon secretion but also influenced by malnutrition and concomitant hepatic dysfunction due to the toxic affect of alcohol. Diagnostic procedures are the measurement of C-peptide-concentrations and profiles of blood glucose after fasting and stimulation with L-arginine or glucose. Especially in the beginning of the endocrine insufficiency the determination of basal levels of blood glucose or C-peptide are not useful. Unless treatment by diet is effective, the therapy of diabetes secondary to chronic pancreatitis should be done by insulin replacement. A certain degree of hyperglycemia may be tolerated due to the risk of hypoglycemia and the persistent alcohol consumption in these patients. Intensified insulin therapy should only be done in selected patients with good compliance. Long-term complications in patients with pancreatogenic diabetes are comparable to diabetes Type I and largely depend on the duration of the diabetes. Life expectancy is reduced, death in these patients is mainly due to persistent alcohol and nicotine abuse (cardiovascular disease, malignant tumors, etc.), in only a minority pancreatitis or diabetes (mainly hypoglycaemia) are relevant risk factors.
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PMID:[Secondary diabetes in chronic pancreatitis]. 1044 9


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