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

Non-diabetic identical twins of insulin-dependent diabetic patients were studied within five years of the diagnosis of their index twin in order to determine whether changes in intermediary metabolism precede the onset of insulin-dependent diabetes mellitus. Two studies were performed: a cross-sectional study of 12 non-diabetic twins and a prospective study of a separate group of 41 non-diabetic twins. Of the 12 twins tested in the cross-sectional study six developed insulin-dependent diabetes and six did not; the six who developed diabetes were given an oral glucose load a mean of 10 months before diagnosis; they then had normal fasting blood glucose levels but worse glucose tolerance than control subjects (120 min post-load (mean +/- SD) blood glucose 8.5 +/- 3.5 vs 4.9 +/- 0.9 mmol/l respectively, p less than 0.05). However, blood lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate and serum insulin levels were similar. In contrast, the six twins in this cross-sectional study who did not develop diabetes and are now unlikely to do so, as a group, had no significant changes compared with the control subjects though one had impaired glucose tolerance. To determine the predictive value of impaired glucose tolerance a separate group of 41 non-diabetic twins was studied prospectively for 8 to 22 years having a total of 147 glucose tolerance tests in this period; in this group six developed diabetes. Eight of the 41 had impaired glucose tolerance; impaired glucose tolerance was found in four of the six who developed diabetes as compared with only four of the 35 who did not (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins. 221 Jan 23

Insulin was found to provoke rapid increases in diacylglycerol (DAG) content and [3H]glycerol incorporation into DAG and other lipids during incubations of rat hemidiaphragms and soleus muscles. Insulin also rapidly increased phosphatidic acid and total glycerolipid labeling by [3H]glycerol, suggesting that insulin increases DAG production at least partly through stimulation of the de novo pathway. Increased DAG production may activate protein kinase C (PKC) as reported previously in the rat diaphragm. We also observed apparent insulin-induced translocation of PKC from cytosol to membrane in the rat soleus muscle. The importance of insulin-induced increases in DAG-PKC signaling in the stimulation of glucose transport in rat diaphragm and soleus muscles was suggested by 1) PKC activators phorbol esters and phospholipase C stimulation of [3H]-2-deoxyglucose (DOG) uptake and 2) PKC inhibitors staurosporine and polymixin B inhibition of insulin effects on [3H]-2-DOG uptake. Although phorbol ester was much less effective than insulin in the diaphragm, phospholipase C provoked increases in [3H]-2-DOG uptake that equaled or exceeded those of insulin. In the soleus muscle, phorbol ester, like phospholipase C, was only slightly but not significantly less effective than insulin. Similar variability in effectiveness of phorbol ester has also been noted previously in rat adipocytes (weak) and BC3H1 myocytes (strong), whereas DAG, added exogenously or generated by phospholipase C treatment, stimulates glucose transport to a degree that is quantitatively more comparable to that of insulin in each of the four tissues. Differences in effectiveness of phorbol ester and DAG could not be readily explained by postulating that the latter acts independently of PKC, because DAG provoked the apparent translocation of the enzyme from cytosol to membranes in rat adipocytes, and effects of DAG on [3H]-2-DOG uptake were blocked by inhibitors of PKC in both rat adipocytes and BC3H1 myocytes. Collectively, our findings provide further support for the hypothesis that insulin increases DAG production and PKC activity, and these processes are important in the stimulation of glucose transport in rat skeletal muscle and other tissues.
Diabetes 1990 Feb
PMID:Effects of insulin on diacylglycerol-protein kinase C signaling in rat diaphragm and soleus muscles and relationship to glucose transport. 222 25

It has been suggested that the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) may be caused by substrate competition between glucose and free fatty acids (FFAs) (Randle's cycle). We measured substrate oxidation and energy metabolism in 10 nonobese untreated NIDDM patients with fasting glucose levels of 7-8 mM with indirect calorimetry in the basal state and during an isoglycemic-hyperinsulinemic (approximately 100 mU/L) clamp without (control) and with a concomitant infusion (approximately 0.35 mmol/min) of Intralipid, a triglyceride emulsion. In the control study, fasting rates of total glucose turnover [( 3-3H]glucose) and glucose and lipid oxidation (9.4 +/- 1.4, 7.3 +/- 1.3, and 3.0 +/- 0.4 mumol.kg-1.min-1, respectively) were comparable with those of nondiabetic individuals. After insulin administration, lipid oxidation was normally suppressed (to 1.3 +/- 0.3 mumol.kg-1.min-1, P less than 0.01), as were the circulating levels of FFA, glycerol, and beta-hydroxybutyrate, whereas glucose oxidation doubled (14.1 +/- 1.8 mumol.kg-1.min-1, P less than 0.01). Because glycemia was clamped at 7.5 mM, endogenous glucose production (EGP) was completely suppressed, and total glucose disposal was stimulated (to 25.7 +/- 5.2 mumol.kg-1.min-1, P less than 0.01 vs. baseline), but glucose clearance (3.6 +/- 0.8 ml.kg-1.min-1) was 30% reduced compared with normal. With concomitant lipid infusion, FFA, glycerol, and beta-hydroxybutyrate all rose during the clamp; correspondingly, lipid oxidation was maintained at fasting rates (3.6 +/- 0.2 mumol.kg-1.min-1, P less than 0.01 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Mar
PMID:Operation of Randle's cycle in patients with NIDDM. 230 95

An increase in glucose concentration in the medium from 5 to 30 mM transiently enhanced diacylglycerol mass and activated protein kinase C in glomeruli isolated from nondiabetic rats as assessed by translocation of enzyme activity from the soluble to particulate fraction. Effects of glucose on both diacylglycerol mass and protein kinase C were evident at 5 and 15 min but waned by 30 min. An increase in glucose concentration in the medium also increased the incorporation of [14C]glucose into the glycerol backbone of diacylglycerol, triacylglycerol, and phospholipids. Several observations implied that [14C]glucose was being incorporated into diacylglycerol through the de novo pathway for glycerolipid synthesis rather than being derived from phospholipids. 1) [14C]glucose incorporation into all the lipids was suppressed by 2-deoxyglucose. 2) The incorporation of [14C]glucose into diacylglycerol and triacylglycerol was evident by 1 min and increased linearly for at least 30 min. In contrast, incorporation into phosphatidylcholine occurred with a lag of at least 5 min. 3) Although only 10% of the [14C]glucose incorporated into lipids was present in diacylglycerol versus greater than 50% in phospholipids, the specific activity of [14C]glucose in diacylglycerol was fivefold higher than that in phospholipid when expressed as a function of mass. 4) Glucose had no effect on labeled diacylglycerol or phosphatidic acid production in glomeruli that had been prelabeled with [3H]glycerol. Glucose-induced increases in diacylglycerol may contribute to the activation of glomerular protein kinase C observed in early diabetes.
Diabetes 1990 Jun
PMID:Increase in diacylglycerol mass in isolated glomeruli by glucose from de novo synthesis of glycerolipids. 234 31

Using an isolated fat cells (IFC) perifusion system and bovine growth hormone (bGH), we demonstrate that the lipolytic response in normal rat IFC is markedly enhanced after preincubation with bGH. In contrast, when IFC are prepared from diabetic animals or in the spontaneous diabetic BB rat (SDR-BB), no such preincubation is necessary. These IFC respond immediately to bGH with maximal release of glycerol. Using a binding assay established for rat growth hormone (rGH) receptors, we measured the number of GH receptors in IFC from these rats. We demonstrate a 75% increase in GH receptors after preincubation with GH in normal rat IFC, and a 125% increase in GH receptors in diabetic IFC, without preincubation. These data support the concept that enhanced sensitivity to GH is an important feature of diabetes in rats and that this sensitivity is at least in part controlled by up-regulation of GH receptors.
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PMID:Growth hormone receptors are up-regulated in diabetic adipocytes. 238 66

Neurosurgical patients with non-ketotic hyperosmolar diabetic coma (NHC) in our institution were analysed retrospectively. Seven cases were diagnosed as NHC being 0.47% of the number of inpatients in the last 5 years. The age ranged from 60 to 72 years old (mean 65) and there were 6 males and 1 female. Only 2 patients (29%) had a clear past history of diabetes mellitus. Prior to the NHC, systemic infection was present in 2 cases. Intravenous hyperalimentation (IVH) was performed in 5 cases, glycerol osmotherapy in 3 cases, diphenylhydantion therapy in 3 cases and tube feeding in 2 cases. The overall mortality rate in our series was 71% (5 cases), of which 2 cases died within 2 days due to cardiopulmonary failure, and 3 cases in the chronic stage died due to disseminated intravascular coagulopathy (DIC), or due to renal failure. The prognosis of NHC in neurosurgical patients is generally bad because of the presence of consciousness disturbance prior to the onset of NHC, which may mask the symptoms occurring from the NHC. Other predisposing factors could be systemic infection, IVH or tube feeding, and osmotic agents which are frequently used in neurosurgical patients. There was a tendency for NHC to occur predominantly in the chronic stage after the blood sugar had returned to normal range from the hyperglycemic state in the acute stage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Non-ketotic hyperosmolar diabetic coma in neurosurgical cases; review of 7 cases]. 240 36

The responsiveness of adipocytes from diabetic rats to lipolytic and antilipolytic stimuli was examined in both an incubation system and a perifusion system. Lipolysis, measured by glycerol release, was initiated with varying concentrations of epinephrine or other agents. Incubated adipocytes prepared from streptozotocin-diabetic rats were more sensitive to low doses of epinephrine than controls, but at higher concentrations of hormone, glycerol release was greater from the control cells. However, maximal lipolytic responses to nonhormonal stimuli, forskolin and methylisobutylxanthine, were clearly greater in incubated adipocytes from diabetic animals. In vivo treatment of both control and diabetic animals with insulin decreased the responsiveness of perifused adipocytes to epinephrine in vitro, further demonstrating the importance of the in vivo hormone levels to lipolytic response of adipocytes. In vitro perifusion with insulin and epinephrine of cells from untreated diabetic animals demonstrated a reduced response to the acute administration of insulin. The interaction of insulin with diabetic adipocytes was further examined by incubating cells with [125I]iodoinsulin and examining the release of intact and degraded hormone during perifusion. The diabetic cells bound more labeled hormone than the control cells, but the release of intact hormone was similar in both types of cells. The diabetic cells, however, released more degraded hormone than did control cells. This suggests that the binding and degradation of insulin in diabetic cells is not impaired and that the decreased responsiveness of these cells to insulin is due to a postreceptor defect. Together these data show that decreased insulin in streptozotocin-diabetes results in increased sensitivity to lipolytic agents. In addition, the diabetes enhances the adipocyte's ability to remove insulin, i.e. increased binding and degradation. Thus, it is likely that the in vitro findings of up-regulation of receptors and increased degradation by the adipocytes are a true reflection of the in vivo insulin deficiency.
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PMID:Hormonal control of lipolysis in perifused adipocytes from diabetic rats. 241 25

Diabetes in rats was induced with streptozotocin (100 mg/kg); myocardial cells (myocytes) were isolated from the hearts 3-4 days later. Diabetic myocytes were characterized as having the same viability and ATP content as control myocytes, but the yield was reduced. The triacylglycerol content of diabetic myocytes was elevated by 3.7-fold; this resulted in an increased rate of glycerol output during subsequent incubations. There was a stoichiometric relationship between the decline in the cellular triacylglycerol content and the release of glycerol into the incubation medium. Isoproterenol stimulated the output of glycerol from control myocytes by about twofold, but the stimulation of glycerol output from diabetic myocytes by isoproterenol was markedly less. The combination of 1-methyl-3-isobutylxanthine with isoproterenol or 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate also failed to produce the same lipolytic response in diabetic myocytes as in control myocytes. Triacylglycerol-loaded myocytes from control rats, prepared by including palmitate in the isolation buffers, were also characterized as having increased basal rates of glycerol output and a reduced lipolytic response to isoproterenol. The level of free fatty acids in diabetic myocytes was 2.8-fold greater than in myocytes from control hearts. The intracellular accumulation of free fatty acids in these quiescent populations of diabetic myocytes may limit the ability of catecholamines to produce a further stimulation of lipolysis.
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PMID:Lipolysis in isolated myocardial cells from diabetic rat hearts. 241 7

Rye flakes, rye bread and white wheat bread were given as suspensions to rats and in standardized breakfast meals to non-insulin-dependent diabetics. In both cases the postprandial glucose response was lower after rye bread than after wheat bread. A larger amount of starch remained in the stomach of the rats 15 min after ingesting rye bread compared to wheat bread, indicating that delayed gastric emptying may be one factor explaining the lower response after rye bread. Although the incremental postprandial glucose areas after rye flakes and wheat bread were similar, the rate of decrease of the glucose curve was slower after flaked rye. This would point to a prolonged absorption of some starch in the rye flakes, also indicated by higher late immunoreactive insulin (IRI) values after that product. In the rats the content of starch in the stomachs 15 min after feeding was higher after rye flakes compared to wheat bread. In vitro incubations with alpha-amylase showed lower availability of the starch in rye flakes than in the breads, indicating that several factors may contribute to the differential postprandial glucose response after the wheat and rye products. The levels of insulin, C-peptide, gastric inhibitory polypeptide (GIP), glucagon, somatostatin, triglyceride and glycerol were followed after the breakfast meals. No pronounced differences of these parameters were seen. However, wheat bread gave significantly higher glucagon and GIP responses than did rye flakes. In conclusion, the absorption pattern and metabolic response after rye bread seems preferable to that after wheat bread. The flaked rye on the other hand was not effective in reducing postprandial glycaemia despite a lower availability of starch in vitro.
Diabetes Res Clin Pract
PMID:Rye products in the diabetic diet. Postprandial glucose and hormonal responses in non-insulin-dependent diabetic patients as compared to starch availability in vitro and experiments in rats. 243 70

Retinal capillary pericyte is a cell type selectively lost in early diabetic retinopathy. The physiological function of pericytes is not yet clearly identified, although it probably has contractile properties. We determined the specific binding of endothelin 1, a 21-amino acid peptide with potent vasoconstrictive action, and the stimulation of diacylglycerol/protein kinase C (DAG/PKC) pathway in cultured retinal capillary pericytes by endothelin. A single specific binding site for 125I-labeled endothelin was identified, with an apparent Kd of 1.3 nM and a maximal binding capacity of approximately 1-2 x 10(5) sites/cell. Endothelin (100 nM) increased total cellular DAG content by 15% at 5 min and 24% at 10 min. When pericytes were labeled isotopically with [3H]glycerol, endothelin stimulated [3H]DAG formation by 100% at 10 min and 88% at 30 min. After 10 min of endothelin treatment, PKC activities were increased by 60 and 100% in the membranous and cytosolic pools, respectively. We conclude that bovine retinal capillary pericytes possess numerous high-affinity specific binding sites for endothelin that mediate the action of endothelin by the stimulation of the DAG/PKC pathway in pericytes. These findings suggest that endothelin is a regulator of the contractile properties of pericytes, which may be adversely affected in diabetic retinopathy.
Diabetes 1989 Dec
PMID:Characterization of endothelin receptors and effects of endothelin on diacylglycerol and protein kinase C in retinal capillary pericytes. 839 Feb 75


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