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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uncontrolled diabetes in rats is associated with reduced levels of both serum somatomedins and hepatic somatomedins. Hepatic somatomedins are recognized after extraction with 5 mol/L acetic acid, have a higher molecular weight (about 30,000) than serum somatomedins (about 8,000), despite acid conditions that dissociate somatomedins from circulating carrier proteins, and stimulate cartilage when given in vivo. To determine if hepatic somatomedins--as potential prohormones--have insulin-like activity comparable with serum somatomedins, their effects on rat epididymal adipose tissue were examined. Somatomedins were prepared from serum and liver extracts by gel filtration on Sephadex G-75, pH 2.4. In initial studies with fat pad segments, extracted hepatic somatomedins increased glucose oxidation only 64 +/- 11% above buffer (mean +/- SEM), while stimulation of 372 +/- 48% was provided by extracted serum somatomedins of comparable cartilage-stimulating potency (P less than 0.01, liver v serum). Further examination was performed with isolated adipocytes in a system sensitive to insulin at a concentration of 10 microU/mL (stimulation 100% above buffer). In dose-response studies measuring glucose oxidation, hepatic somatomedins had insulin-like activity of 16 microU/mL versus 55 microU/mL for serum somatomedins equipotent on cartilage (P less than 0.05); measuring glucose incorporation into total lipids, hepatic somatomedins had undetectable activity while serum somatomedins had activity of 28 microU/mL. It is concluded that hepatic somatomedins with potent cartilage-stimulating activity have greatly reduced insulin-like activity. The apparent dissociation in biologic activity of hepatic somatomedins suggests that while they may be prohormones, they may also represent a class of growth factors separate from the circulating somatomedins.
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PMID:Nutrition and somatomedin. X. Comparison of insulin-like activity of somatomedins extracted from liver and serum. 641 11

Insulin deficiency was produced by streptozotocin in young (5-6 wk old) male rats, and measurements were made of plasma triglyceride and glucose concentrations and of lipoprotein lipase (LPL) activity of adipose tissue (epididymal) and muscle (gastrocnemius and soleus). Rats with streptozotocin-induced diabetes underwent a significant reduction in adipose tissue LPL activity (both total and heparin releasable), but the fall in LPL activity in these rats bore little relationship to their rise in plasma triglyceride concentration. Furthermore, muscle LPL activity was essentially unchanged in diabetic rats. Qualitatively similar changes were observed when measurements were made at either 8 a.m. (after the normal evening access to food) or 2 p.m. (6 h after food withdrawal). It is concluded that the hypertriglyceridemia that occurs secondary to insulin deficiency is not a simple function of decreased tissue LPL activity.
Diabetes 1980 Aug
PMID:Dissociation between plasma triglyceride concentration and tissue lipoprotein lipase deficiency in insulin-deficient rats. 644 94

The effect of adebit (N-butylbiguanide) on the rat tissues in vitro, namely, on sugar consumption and transport, glucose oxidation, as well as on gluconeogenesis in the rat organism, was studied. Glucose consumption and D-xylose transport in the diaphragms of intact animals and glucose consumption and oxidation in the epididymal fat of rats, given hydrocortisone, were determined. Gluconeogenesis intensity under adebit action was investigated according to the blood sugar level following adrenaline injections to rats after 24-hour fasting. It was established that the administration of adebit at concentrations of 0.2 to 0.5 mM results in intensified insulin-independent glucose consumption and xylose transport in the diaphragm, the maximum transport rate being augmented and the dissociation constant remaining unchanged. It is concluded that adebit does not change the properties of sugar transmitter, but influences the cell metabolism by inhibiting oxidative phosphorylation. The use of adebit in therapeutic concentrations (5 to 10 mcM) gave an insulin-dependent rise of glucose consumption and oxidation in the fatty tissue by 44%. A decrease in the blood sugar level in the presence of adrenaline hyperglycemia under the action of adebit therapeutic doses was not observed. It is concluded that biguanide hypoglycemizing action in diabetes mellitus is based on the biguanide potentiated insulin effectiveness.
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PMID:[Effect of adebit (N-butylbiguanide) on the metabolism and oxidation of glucose in rat tissues in vitro]. 651 86

Evidence from a number of laboratories has suggested that the mechanism of insulin action involves the release of an intracellular mediator polypeptide from the plasma membrane. It has been proposed that activation of a protease with trypsin-like specificity is involved in release of the putative mediator. In an effort to assess the potential role of such a protease in intact cells, the present study tested the effects of a variety of low-mol-wt protease inhibitors on insulin's metabolic action in isolated rat epididymal fat cells. The protease inhibitors studied included p-aminobenzamidine, benzamidine, phenylguanidine, diisopropylfluorophosphate, leupeptin, and the competitive substrate N-alpha-tosyl-L-arginine methylester. Leupeptin was devoid of activity. Most of the other inhibitors used were able to interfere with insulin-stimulated metabolism if used in sufficiently high concentrations, concentrations considerably higher than those required for inhibition of known proteases or inhibition of intracellular processes in a previously described system which involves a trypsin-like enzyme. Moreover, they displayed various activities unrelated to protease inhibition that could explain their effects on insulin action better than protease inhibition. While none of the data on individual inhibitors were by themselves convincing enough to either confirm or reject the hypothesis concerning the involvement of a protease with trypsin-like specificity in insulin action, taken together our results do weaken the hypothesis considerably and in particular render the involvement of an extracellular trypsin-like enzyme improbable.
Diabetes 1982 Nov
PMID:On the mechanisms of inhibition of insulin action by small-molecular-weight trypsin inhibitors. 675 16

Poor growth in uncontrolled experimental diabetes appears due in part to increased circulating inhibitor, a factor (or factors) that blocks stimulation of growing cartilage by somatomedins. To determine if the inhibitor has other antianabolic properties, we examined effects on insulin and insulin-like action on muscle and adipose tissue. Rat epididymal fat pads were exposed to normal rat serum, somatomedins (fraction from normal rat serum) or insulin, with or without added streptozotocin-diabetic rat serum or inhibitor (fraction from diabetic serum); insulin-like activity was assessed by glucose conversion to CO2. Diabetic rat serum alone lowered glucose utilization significantly below buffer levels (P less than .010), but inhibitor alone had no effect. However, stimulation by insulin, normal rat serum, or somatomedins was decreased significantly by both diabetic rat serum or inhibitor (P less than 0.01); Lineweaver-Burk analysis suggested that such inhibition was noncompetitive. In incubations with rat diaphragm, neither diabetic rat serum nor inhibitor alone lowered glucose incorporation into glycogen, but both inhibited muscle stimulation by insulin (P less than 0.01). In in vivo studies, rats given insulin with added diabetic rat serum exhibited decreased stimulation of glucose incorporation into muscle glycogen (P less than 0.01) and into adipose tissue total lipids. These observations indicate that an inhibitor in the serum of diabetic rats can brake anabolic processes is muscle (glycogen formation) and adipose tissue (glucose utilization, lipid formation). Such an inhibitor may therefore contribute to poor growth in diabetes by decreasing calorie storage due to insulin and insulin-like actions as well as skeletal elongation due to somatomedin action.
Diabetes 1982 Feb
PMID:Nutrition and somatomedin. IX. Blunting of insulin-like activity by inhibitor in diabetic rat serum. 675 35

The present studies have been designed to evaluate the effects of physical training in rats with a diminished insulin reserve. Mild diabetes mellitus was induced in rats with 45 mg/kg streptozotocin. Physical training was done on a treadmill, with a progressive program, twice daily, 5 days per week, for 10 wk in control and diabetic rats. At the end of the training program, a significant diminution in body weight gain and in epididymal fat pad weight was observed in both trained groups, as compared with sedentary controls. Sixty-four hours after the last exercise, control (N = 16), control-trained (N = 14), diabetic (N = 17), and diabetic-trained (N = 15) rats were submitted to an intravenous glucose tolerance test (0.5 g/kg). Arterial blood samples were collected at -15, 0, 2, 4, 6, 10, 15, 30, 45, and 60 min during the test in unanesthetized and precannulated rats for plasma glucose and insulin determinations. In normal rats, physical training induced a sharp decrease in the basal insulin levels (36 +/- vs. 101 +/- 6 microunits/ml; P less than 0.001) without any significant changes in glucose levels (122 +/- 4 vs. 129 +/- 2 mg/dl; P less than 0.05). After the glucose loading there was no significant change in the glucose tolerance curve, although the insulin values remained lower throughout the test in the trained group. In the diabetic rats, the elevated basal glucose levels were significantly diminished in the trained group as compared with the untrained diabetic group (177 +/- 22 vs. 306 +/- 37 mg/dl; P less than 0.001), although the basal insulin values were similar in both groups (51 +/- 7 vs. 54 +/- 9 microunits/ml; P greater than 0.05). The improvement in the glucose tolerance of the diabetic-trained rats was further confirmed by the glucose disappearance rate constant that was significantly increased (3.6 0.4 vs. 2.0 +/- 0.3; P less than 0.01), although not fully restored to normal (6.3 +/- 0.2; P less than 0.001). These data clearly show that in rats with a diminished insulin reserve, a 10-wk running program greatly improved the glucose homeostasis. Measurements of circulating insulin suggest that, although an effect on insulin secretion cannot be totally excluded, the beneficial effect of physical training on diabetes mellitus is probably best explained by an increase in insulin sensitivity.
Diabetes 1982 May
PMID:Beneficial effects of physical training in rats with a mild streptozotocin-induced diabetes mellitus. 675 57

The influence of insulin on the intracellular free sodium and potassium ion concentrations ([Na+]i, [K+]i) and resting membrane potential of rat epididymal adipocytes was examined to determine its potential for mediating insulin's action on other cellular processes. Direct intracellular measurements of [Na+]i, [K+]i, and the resting membrane potential were made using ion-selective and conventional microelectrodes. The use of these microelectrodes enabled us to continuously monitor these parameters in the same cell before, during, and after periods of insulin stimulation of up to 20-min duration. The electrical potentials measured in these experiments remained unchanged when the cells were stimulated with insulin (0.01, 0.1, or 1.0 mU/ml). Varying the extracellular glucose concentration had no effect on these results. Our results provide the first direct measurement of [Na+]i and [K+]i in adipose tissue and clearly demonstrate that the response to insulin's association with its receptors on the cell surface and subsequent action on hexose transport and cellular metabolism does not involve a change in membrane potential or intracellular sodium and potassium ions.
Diabetes 1980 Dec
PMID:Insulin does not act by causing a change in membrane potential or intracellular free sodium and potassium concentration of adipocytes. 700 70

In view of the known effect of zinc on the crystalline nature of insulin, we have investigated whether zinc alters the biologic potency of this hormone. Using the rate of lipogenesis by rat epididymal adipocytes as an index of the biologic potency of insulin, we have shown that zinc exerts a potent stimulatory effect upon lipogenesis in vitro similar to, but quite independently of, insulin and that it has an additive effect with that of insulin when both are incubated together. This effect of zinc on adipocytes and the biologic potency of insulin, hitherto unreported, is of significance at the biologic, pharmacologic, and clinical level.
Diabetes 1980 Aug
PMID:Insulin-like effect of zinc on adipocytes. 700 79

Rats were fed ad libitum a 40% fat diet containing either 30% sucrose or 30% starch by weight for 8-9 weeks. Insulin levels during a meal tolerance test were significantly greater in rats fed sucrose than in rats fed starch, but serum glucose levels were not affected by diet and tended to decrease as time after the meal increased. Insulin levels during an oral glucose tolerance test were significantly greater in the rats fed sucrose. Serum glucose levels were not affected by diet. Body weights and epididymal and perirenal fat pad weights were higher in rats fed sucrose than in rats fed starch. Serum triglyceride and cholesterol levels were not different. These results show that relatively low sucrose levels in a high fat diet can produce higher insulin levels than starch before and after either a glucose load or a meal. This relative insulin resistance is symptomatic of onset diabetes.
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PMID:Effects of feeding rats sucrose in a high fat diet. 700 6

Biosynthetic human insulin (BHI) obtained from separately synthesized A- and B-chains by recombinant DNA technology with Escherichia coli fermentation was compared with human and pork insulin of high purity in vitro. Applying four biologic tests (glucose oxidation and glucose incorporation into the lipids by rat epididymal fat pads, inhibition of lipolysis, and ATP depletion of isolated fat cells) and three receptor assays (binding competition with human fat cells, IM-9 lymphocytes, and rat liver cell plasma membranes), we could not discern significant differences of the half-maximum response by these seven methods. The only variance occurred with the ATP-depletion assay. This method disclosed 10% greater maximum reversion of isoproterenol-induced ATP depletion by BHI when compared with pork insulin.
Diabetes Care
PMID:Potency of biosynthetic human insulin determined in vitro. 701 33


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