Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether synthetic somatostatin originally isolated from sheep hypothalamus can inhibit hormone secretion in the same species, we measured plasma levels of GH, insulin, glucagon, and glucose of normal sheep under a variety of experimental conditions in the presence and absence of somatostatin infusion. An oral dose of 2.5 mg./kg. 3,5-dimethypyrazole increase plasma GH from 10.9 to 376.9 ng. per milliliter, which was suppressed by 50 per cent and 80 per cent with 0.5 and 1 mg. synthetic cyclic somatostatin, respectively. Linear somatostatin (0.5 mg.) was without effect in two animals tested. Propionate (0.5 mmole per kilogram) and arginine (10 gm.) induced a rise in plasma insulin and GH, and glucagon was effectively blocked by cyclic somatostatin (0.5 mg.). Similarly, somatostatin inhibited glucose, and glucagon provoked GH and insulin secretory responses without affecting glucose or FFA levels. Somatostatin had no effect on the disappearance of injected glucagon. Finally, addition of somatostatin to incubation media prevented PGE promoted GH release, and suppressed cyclic AMP accumulation, although to a lesser extent, in sheep anterior pituitary pieces. In view of the large amounts required to suppress stimulated hormone release and the general lack of specificity of somatostatin, it is suggested that this peptide may have a functional role only in the release of hormones of the pituitary, where it could occur in relatively high local concentrations. Its inhibition of extrapituitary hormone secretion may be purely a pharmacologic effect that, nevertheless, suggests an interference with a step common to the secretory process of hormones.
Diabetes 1975 Sep
PMID:Studies on growth hormone secretion. VII. Effects of somatostatin on plasma GH, insulin, and glucagon in sheep. 16 76

An "endoneurial" preparation from a rabbit tibial nerve fascicle was used to study the ability of peripheral nerve axons and Schwann cells to derive their composite energy requirements from glucose, D-beta-hydroxybutyrate, or albumin-bound palmitate, and the effects of insulin in vitro on their composite glucose utilization. Samples incubated with 5 mM glucose for 2 h maintained a stable O2 uptake and P-creatine and ATP concentrations, and they exhibited a slight increase in P-creatine/creatine ratio (the electron microscopic appearance of the preparation was previously shown to be unaltered under these conditions). The rate of glucose oxidation required to account for the O2 uptake accounted for 61% of the glucose uptake. In samples incubated without substrate for 2 h, a marked fall in tissue glucose was associated with a 50% decrease in O2 uptake and with decreases in P-creatine, ATP, and in the P-creatine/creating ratio. In medium lacking glucose but containing 5 mM DL-beta-hydroxybutyrate, a stable rate of D-beta-hydroxybutyrate uptake was observed, and acetoacetate production accounted for only a small fraction; significant decreases in O2 uptake or ATP were prevented, and, although P-creatinde and the P-creatine/creatine ratio fell, they remained significantly higher than after incubation without substrate. An efficient blood-nerve barrier to albumin is known to exist. Medium containing albumin-bound palmitate with molar ratios or palmitate/albumin of 1 or 2 (highest FFA concentration, 1.32 meq/L) failed to prevent decreases in P-creatine, ATP, and in the P-creatine/creatine ratio during incubations without glucose; the associated O2 uptakes suggested that the tissue is susceptible to respiratory uncoupling and depression son exposure to albumin-blund palmitate as compared with non-neural tissue. Insulin (100 or 1000 microU/ml) had no detectable effects on glucose utilization in the endoneurial preparation during 2-h incubations with 5 mM glucose or (U-14C) glucose. In contrast, in epineurial tissue from rabbit sciatic nerve, insulin (100 micronU/ml) increased (U-14C) glucose incorporation into CO2 and total lipid. The neural components of peripheral nerve are probably dependent on glucose as their major substrate for energy production and respiration under most physiologic conditions in which elevated plasma ketone body concentrations are absent; their composite glucose utilization is not subject to acute, direct regulation by insulin in concentrations that might reasonably be derived from plasma insulin of pancreatic origin.
Diabetes 1979 Oct
PMID:In vitro studies of the substrates for energy production and the effects of insulin on glucose utilization in the neural components of peripheral nerve. 47 82

The interrelation of enlarged body fat mass (BFM) with reduced carbohydrate tolerance and hyperinsulinemia was studied in obese subjects with chemical diabetes. These patients were subjected to lipectomy following weight loss induced by a low-calorie, low-carbohydrate diet. An improvement in glucose tolerance and in insulin sensitivity and a reduction in insulin release during OGTT was observed after a diet-induced BFM loss of 9.9 +/-1.2 kg. Subsequent surgical reduction of BFM by 6.0 +/- 0.5 kg had no further effect upon carbohydrate tolerance, insulin release or insulin sensitivity though a marked decrease in basal plasma FFA values was observed. These findings suggest that fat mass enlargement per se has no effect on blood glucose homeostasis after oral or i.v. loading. The improvement in carbohydrate tolerance and in insulin resistance usually observed following diet-induced loss of BFM seems to be due to the reduction in calorie and carbohydrate intake rather than to decrease of BFM.
 ...
PMID:Effects of fat mass reduction by dieting and by lipectomy on carbohydrate metabolism in obese patients. 48 64

The influence of exercise on forearm muscle metabolism was examined in 9 healthy subjects, in 16 diabetics and in 4 obese subjects during complete starvation. During exercise glucose uptake rose 7-8 fold in the controls. However, no increase of glucose uptake was observed in the other groups studied. Moreover, a glucose production from the working muscle took place in about 40 percent of both the diabetic patients and the starved obese subjects. The nonutilization of glucose during physical work in the diabetic like states was accompanied by a significantly diminished lactate output. The arterial concentration of FFA, glycerol beta-HOB and Acac was markedly elevated in the starved obese patients. The FFA-uptake at rest and during exercise, however, was not different from results of controls. Whereas an effux of beta-HOB has been observed during exercise, Acac uptake was increased in these patients. It is suggested that in maturity onset and starvation diabetes glycolysis is inhibited.
 ...
PMID:Muscle metabolism during exercise in diabetics and in obese during starvation. 68 Jun 26

Plasma FFA, glucagon, insulin, glucose, and growth hormone were followed every hour during 24 hours of saline infusion, 24 hours of somatostatin (4mg.) infusion, and three hours without infusion in six nonobese and six obese maturity-onset diabetic men. Somatostatin induced the same changes in the parameters of both groups of diabetic patients: A rise in plasma FFA, which gradually disappeared after some hours of infusion, a suppression of plasma glucagon and insulin, and an augmentation of plasma glucose both postprandially and during the night. Plasma growth hormone was suppressed in the nonobese patients, but somatostatin could not further suppress the low and nonfluctuating plasma growth hormone concentration in the obese maturity-onset diabetics. The results indicate that a preparation with a pattern of hormone suppression like that of somatostatin will not be useful in the control of maturity-onset diabetes, because it suppresses insulin and elevates the blood glucose concentration.
Diabetes 1978 Oct
PMID:Somatostatin in maturity-onset diabetes. 70 Feb 57

The changes in the content of STH and FFA in the blood and of catecholamines in the urine under the effect of insulin hypoglycemia were studied in 28 insulin-sensitive and 40 insulin-resistant patients suffering from diabetes mellitus. Patients with diabetes mellitus who needed 100 or more insulin units per 24 hours for compensation of the affection were referred to the insulin-resistant ones. In these cases a less pronounced elevation of the blood STH level and of urinary catecholamines was noted in response to insulin hypoglycemia. This was accompanied by a considerable reduction of lipolysis in the insulin-resistant patients. It is suggested that in the insulin-resistant patients, due to reduction of the STH and catecholamine stimuli, FFA is incapable of providing the necessary energy balance at the cellular level in insulin insufficiency. This accounts for an increased requirement in exogenous insulin in the insulin-resistant patients with diabetes mellitus. Reduction of the FFA and catecholamine reserves in the insulin-resistant patients suffering from diabetes mellitus is postulated to be one of the main factors in the resistance pathogenesis.
 ...
PMID:[Dynamics of levels of growth hormone and free fatty acids in the blood, and catecholamines in the urine of insulin-resistant and insulin-sensitive diabetes mellitus patients during insulin hypoglycemia]. 72 70

Studies of fat mobilization and transport are reported in six patients with the Prader-Willi syndrome. Two patients had carbohydrate intolerance. One of these had a low and the other an augmented insulin response to glucose challenge. Following challenge with glucose, three of the four nondiabetics had normal insulin responses or increased responses consistent with their obesity; the other nondiabetic had insulinopenia. Measurements of the effects of norepinephrine, insulin, glucose, and 5-methylpyrazole-3-carboxylic acid on plasma levels of FFA, glycerol, and ketones provide no evidence for abnormal regulation of mobilization of fat from adipose tissue. Measurements of plasma lipids and postheparin lipolytic activity are consistent with normal uptake of fat into adipose tissue, and normal fatty acid composition of adipose tissue gives no evidence for abnormal lipogenesis.
Diabetes 1977 Sep
PMID:The Prader-Willi syndrome. Regulation of fat transport. 89 39

Pancreatectomized dogs developed hypertriglyceridemia. This probably resulted from a lack of insulin rather than a lack of glucagon, as it did not develop either in pancreatectomized dogs maintained on insulin, or in dogs with all but the uncinate process of the pancreas removed. The increase in plasma triglycerides was preceded by a decrease in post-heparin lipolytic activity (PHLA) and an increase in FFA. As the hypertriglyceridemia developed in fasted dogs who had previously been on fat-free diets, the triglyceride fatty acids (TGFA) were nondietary. These endogenous TGFA originated from adipose tissue rather than from de novo synthesis. The composition of the lipoprotein TGFA was identical to that of adipose tissue. Furthermore, nicotinic acid blocked the FFA increase and the development of the hypertriglyceridemia. However, it did not prevent the fall of PHLA. Although their TGFA were entirely nondietary, the lipoproteins in these diabetic dogs resembled chylomicrons in their electrophoretic mobility, size, density, and composition. Surgical, histological and tracer studies suggested that in addition to the liver, the intestinal mucosa makes these lipoproteins. The tracer studies also suggested that circulating FFA might enter the intestinal mucosal cells directly and be esterified.
Diabetes 1975 Mar
PMID:Production of chylomicron-like lipoproteins from endogenous lipid by the intestine and liver of diabetic dogs. 111 49

The present study was undertaken to determine whether alterations in ketone body utilization and hepatic production, independent of the FFA load, were also involved in the development of fasting ketosis. Plasma Beta-OH butyric acid (Beta-OHB) increased to 2.5-4.5 mM and plasma FFA to 1,000-1,400 muEq/L. in normal weight individuals after five to seven days' starvation and in obese subjects after ten to fourteen days' fasting. Acute elevations fo the plasma FFA greater than 1,500 muEq/L. for sixty minutes in fed normal weight and obese subjects with a fat meal-heparin regimen resulted in peak elevations of plasma Beta-OHB (0.25-0.45mM), only 10 percent of that seen during fasting. When plasma FFA were lowered acutely during fasting with the antilipolytic agent Pyrazole to control levels (400-600 muEq/L.), plasma Beta-OHB decreased 35 plus or minus 5 per cent. Comparable lowering of plasma FFA in normal weight or obese starved subjects given dexamethasone to maintain elevated fasting plasma insulin levels resulted in an 87 plus or minus 3 per cent decrease in plasma Beta-OHB. Similar studies in obese fasted subjects pretreated with an intravenous infusion of insulin (1.0 U/hr. for eight hours) before receiving Pyrazole resulted in a 65 plus or minus 5 per cent decrease in plasma Beta-OHB. Plasma Beta-OHB half-life, determined after injections of 12 gm. Beta-OHB, increased significantly during fasting (110 plus or minus 15 minutes) and was decreased when the fasting subjects were maintained on dexamethasone (65 plus or minus 7 minutes). These studies indicate that accelerated hepatic ketogenesis during starvation is a result of both enhanced activity of the enzymatic system(s) involved in ketone body production as well as an increased FFA load. The increase in plasma Beta-OHB during fasting reflects not only an accelerated rate of hepatic ketogenesis but also an impairment of peripheral utilization, both processes apparently being sensitive to insulin. Diabetes 24:10-16, January, 1975.
Diabetes 1975 Jan
PMID:Physiologic mechanisms in the development of starvation ketosis in man. 112 May 41

The use of continuous indirect calorimetry in the course of a 100 g OGTT in 10 normal subjects has shown that carbohydrate oxidation rises with the secondary fall in blood glucose, suggesting that it could result from glucose stored under the influence of insulin. The experimental increase in FFA by a neutral fat infusion in 8 normal subjects decreased this oxidation in spite of the insulin rise. In a group of 5 non-obese, non-ketotic insulin-deficient diabetics, carbohydrate oxidation was found to be normal and directly correlated with plasma glucose levels. On the other hand, in 7 obese diabetics with high plasma insulin levels carbohydrate oxidation was found to be low, suggesting that carbohydrate intolerance could result from the non-oxidation of glucose. This study shows heterogeneity of diabetes, since glucose intolerance could result from non-oxidation of glucose as well as from insufficient pancreatic secretion.
 ...
PMID:[Measurement of carbohydrate oxidation by means of indirect continuous calorimetry in normal and diabetic subjects]. 112 56


1 2 3 4 5 6 7 8 9 10 Next >>