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

The effects of insulin deprivation and replacement on adipose tissue metabolism were investigated in vivo with microdialysis in nine insulin-dependent diabetic patients with no residual insulin secretion. Dialysis probes, implanted in abdominal subcutaneous fat, were continuously perfused, and tissue dialysate concentrations of glycerol (lipolysis index), glucose, lactate, and pyruvate were determined. Comparisons were made with respective metabolite levels in venous plasma. After termination of intravenous insulin infusion, free insulin in plasma fell from 130 to 70 pM. At the same time, glucose levels in plasma and adipose tissue rose in parallel. However, the relative increase in glucose levels was greater in adipose tissue than in blood. On the other hand, the increase in glycerol concentration in adipose tissue (35%) was markedly less than that in venous plasma (250%). Lactate and pyruvate levels in adipose tissue and blood remained unchanged. After the resumption of intravenous insulin, free insulin in plasma rose to approximately 600 pM. At the same time, the glucose levels in blood and adipose tissue decreased rapidly, and the glycerol concentration in these tissues decreased to 50% of the baseline levels. The lactate and pyruvate levels in subcutaneous tissue increased briefly after insulin replacement, whereas the lactate but not pyruvate levels in blood showed a similar increase. The alpha- or beta-blocking agents phentolamine and propranolol in the ingoing tissue perfusate did not influence tissue glycerol at any time during the experiment. We concluded that insulin-induced changes in circulating metabolites only partly reflect variations in adipose tissue substrate kinetics. During insulin deprivation, glucose is accumulated in the adipose tissue extracellular compartment, probably because of reduced utilization by the adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Jun
PMID:Effects of insulin deprivation and replacement on in vivo subcutaneous adipose tissue substrate metabolism in humans. 204 Mar 82

We investigated the effects of infusion of a 20% triglyceride emulsion plus heparin (LH) on carbohydrate (CHO) metabolism during basal insulin and glucose turnover conditions in normal male subjects. In study 1, LH or saline was infused at 0.5 and 1.5 ml/min for 2 h each. Plasma free fatty acids rose from approximately 0.4 to 0.8 mM with the low rate and to between 1.6 and 2.1 mM with the high rate. Similar increases occurred in plasma concentrations of glycerol, acetoacetate, and beta-hydroxybutyrate. LH infusions resulted in significant increases in C-peptide concentrations but had no effects on any of the other measured parameters of CHO metabolism. In study 2, LH or saline was infused as in study 1, but the compensatory insulin release was prevented by intravenous infusion of somatostatin and replacement of basal insulin and glucagon concentrations. This resulted in significant increases in plasma glucose (from 4.5 +/- 0.2 to 7.1 +/- 0.6 mM, P less than 0.001) and hepatic glucose output (from 9.0 +/- 1.5 to 11.3 +/- 1.4 mumol.kg-1.min-1, P less than 0.05) and a decrease in glucose clearance (from 2.32 +/- 0.13 to 1.44 +/- 0.11 ml.kg-1.min-1, P less than 0.05). We conclude that lipids can have adverse effects on CHO metabolism under basal conditions and that healthy individuals can compensate for these effects with additional secretion of insulin.
Diabetes 1991 Jun
PMID:Effects of lipid on basal carbohydrate metabolism in normal men. 204 Mar 85

We compared regional cerebral blood flow (rCBF) and arteriojugular vein differences of glucose, ketones, glycerol, lactate, pyruvate, and O2 in eight subjects with well-controlled insulin-dependent diabetes mellitus (IDDM) and in six healthy volunteers. Duration of diabetes was 19.4 +/- 2.1 yr. Measurements were performed before and after 120 min of insulin infusion and concomitant Biostator-controlled normoglycemia. Net uptake of ketones was seen in IDDM subjects before but not after insulin. Net uptake of glucose did not differ significantly between groups. During normoglycemia the molar ratio of O2 to glucose uptake was lower in IDDM than in nondiabetic subjects (4.68 vs. 5.50; P less than 0.05; Wilcoxon test). Small but significant release of lactate and pyruvate was seen in IDDM but not in nondiabetic subjects. The rCBF was measured by 11CH3F and position emission tomography. Global mean CBF was higher in IDDM subjects (64.9 +/- 5.9 vs. 49.3 +/- 2.7 ml.100 g-1.min-1, means +/- SE in nondiabetic subjects, P less than 0.05). rCBF was enhanced in many cortical and subcortical areas, whereas it was decreased in the head of the caudate nucleus. Neuropsychological testing did not reveal obvious cognitive dysfunction. The results imply that a larger fraction of glucose is nonoxidatively metabolized in the IDDM subjects and furthermore indicate an abnormal rCBF pattern in these subjects.
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PMID:Cerebral blood flow and substrate utilization in insulin-treated diabetic subjects. 211 Apr 24

The extrapancreatic effects of sulfonylurea drugs include increased glucose uptake by certain peripheral tissues. To study this effect, we used BC3H1 myocytes, which are reported to respond to these drugs. Within 30 min, tolbutamide and glyburide increased [3H]-2-deoxyglucose uptake in a dose-dependent manner. The inactive analogue carboxytolbutamide had no effect on glucose transport. Because increases in glucose transport may be mediated by activation of the diacylglycerol-protein kinase C signaling system, we examined the effects of these drugs on lipid metabolism and protein kinase C activity. Unlike insulin, tolbutamide and glyburide failed to increase [3H]glycerol labeling of diacylglycerol or labeling of phospholipids by 32P. After 30 min of treatment with tolbutamide or glyburide, however, membrane-associated and cytosolic protein kinase C activity were each increased. When cells were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 48 h to deplete certain isoforms of protein kinase C, glyburide, tolbutamide, and acute TPA treatment failed to increase glucose uptake, suggesting that TPA and sulfonylureas operate through activation of a common pathway. The effect of glyburide was additive to TPA in stimulating glucose uptake at low but not high TPA concentrations. As with insulin and TPA, extracellular Ca2+ was not essential for sulfonylurea-stimulated glucose uptake. Staurosporine, a protein kinase C inhibitor, blocked glyburide-, tolbutamide-, and insulin-stimulated glucose uptake. In intact cells, glyburide stimulated the phosphorylation of both 80,000-Mr and 40,000-Mr proteins, which are markers for protein kinase C activation. Addition of sulfonylureas directly to the protein kinase C assay system in vitro provoked dioleinlike effects, in that sensitivity of the enzyme to Ca2+ was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Nov
PMID:Sulfonylurea-stimulated glucose transport association with diacylglycerollike activation of protein kinase C in BC3H1 myocytes. 212 69

To study insulin action on intermediary metabolism in relation to glucose disposal in Type 1 (insulin-dependent) diabetes, 29 patients and 15 control subjects underwent sequential euglycemic clamps (insulin infusion rates 0.5, 1.0, 2.0 and 5.0 mU.kg-1.min-1 in 2 hour periods). Dose-response curves were constructed for insulin-stimulated glucose disposal. Metabolite profiles were determined in the basal state, and during submaximal (+/- 80 mU/l) and maximal (greater than 500 mU/l) insulinaemia. For at least 11 hours preceding the study, blood glucose levels were maintained between 4 and 10 mmol/l in the patients. In the basal state, when at matched glycemia hepatic glucose production is known to be similar in patients and control subjects, glucose, glycerol, free fatty acids and glucagon were comparable, whereas differences were found for alanine (-29%, diabetic vs. control subjects), lactate (-24%), acetoacetate (+270%), 3-hydroxybutyrate (+260%) and insulin (+210%; all p less than 0.02). At submaximal (+/- 80 mU/l) and maximal (greater than 500 mU/l) insulin levels, metabolite levels were comparable, except alanine (-20% diabetic vs. control subjects, p less than 0.001). Glucose disposal rates, however, were decreased in patients at submaximal insulin levels (ED50 73 +/- 10 vs. 54 +/- 4 mU/l in control subjects, p less than 0.01 whereas maximal glucose disposal was similar (61 +/- 3 vs. 65 +/- 3 mumol.kg-1.min-1). In conclusion, in Type 1 diabetes: (a) changes in basal levels of intermediary metabolites were present, despite 11 hours of antecedent euglycemia; (b) in contrast to glucose disposal at submaximal insulinaemia, no major difference existed in insulin's efficacy on intermediary metabolism.
Diabetes Res 1990 Sep
PMID:Insulin resistance in type 1 (insulin-dependent) diabetes: dissimilarities for glucose and intermediary metabolites. 213 95

Intravenous glucose tolerance was measured at diagnosis and during the subsequent 10 years in 103 Type 2 diabetic patients not treated with insulin. KG (the rate constant for clearance of intravenous glucose) was inversely related to fasting plasma glucose at all review times (at diagnosis being Rs = -0.77, p less than 0.001), and at times to the circulating concentrations of ketone bodies (at diagnosis being Rs = -0.52, p less than 0.001) and glycerol (Rs = -0.29, p less than 0.01). In the first year of treatment, most metabolic abnormalities improved. One to 10 years after diagnosis, fasting glucose concentration and intravenous glucose tolerance deteriorated (median glucose from 6.4 to 7.4 mmol l-1, p less than 0.001; median KG from 0.81 to 0.69% min-1, p less than 0.01). Likewise, the 'homeostatic model assessment' of insulin insensitivity deteriorated (median from 2.3 to 3.7 arbitrary units, p less than 0.001) over the same period but first-phase insulin secretion remained steady or improved. This suggests that increases in insulin insensitivity have a predominant effect on slowly deteriorating glucose tolerance from 1 to 10 years after diagnosis in Type 2 diabetes.
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PMID:The metabolic associations of intravenous glucose tolerance in the 10 years from diagnosis of type 2 diabetes. 214 34

Glomerular hyperfiltration is a characteristic feature of insulin-dependent diabetes. We examined the relative roles of renal size, as well as glycemic parameters (HbA1c, glycosylated albumin, plasma glucose) in addition to growth hormone, somatomedin C, beta-hydroxybutyrate, alanine, and glycerol in determining the glomerular filtration rate (GFR). Sixty-two insulin-dependent patients with normal urinary albumin excretion rates (AER less than 15 micrograms/min), who were less than 50 years of age, were included in the study. Data were subjected to multiple regression analysis with GFR as a dependent variable. Renal volume was the primary statistical determinant of hyperfiltration, but HbA1c also significantly correlated with GFR. No correlation was found with glycosylated albumin or blood glucose, but RPF correlated strongly with GFR, and borderline correlation was found between renal volume and HbA1c. Renal hyperfiltration, defined as a GFR greater than 150 ml/min, was found in approximately 50% of patients with HbA1c values greater than 9.5%. Other studies suggest that such patients have a much higher risk of developing clinically evident diabetic nephropathy over the ensuing years. Renal volume appears to be the major determinant of GFR, but long-term metabolic control, as evidenced by the level of HbA1c, also contributes, partly independent of renal volume. Short-term metabolic control, as evaluated by blood glucose and serum-fructosamine, did not correlate with GFR. We suggest that exact determination of GFR and renal volume should be included in long-term prospective controlled intervention trials in patients with insulin-dependent diabetes mellitus (IDDM).
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PMID:Renal and glycemic determinants of glomerular hyperfiltration in normoalbuminuric diabetics. 215 Dec 27

We investigated the vascular response (blood flow and resting vascular resistance) and the metabolic response (exchange of metabolites and respiratory gases) to local insulin administration in the forearms of healthy young volunteers with the use of the perfused-forearm technique. In the postabsorptive state, the deep tissues of the forearm (mostly skeletal muscle) took up glucose (mean +/- SE 1.09 +/- 0.17 mumol.min-1.dl-1 forearm vol), beta-hydroxybutyrate (0.267 +/- 0.130 mumol.min-1.dl-1), and O2 (9.96 +/- 1.02 mumol.min-1.dl-1) and released lactate (0.284 +/- 0.098 mumol.min-1.dl-1), glycerol (0.029 +/- 0.012 mumol.min-1.dl-1), citrate (0.091 +/- 0.030 mumol.min-1.dl-1), alanine (0.184 +/- 0.044 mumol.min-1.dl-1), CO2 (7.36 +/- 0.97 mumol.min-1.dl-1), and protons (12.1 +/- 1.4 pmol.min-1.dl-1). Forearm blood flow (by venous occlusion plethysmography) was 2.95 +/- 0.18 ml.min-1.dl-1, and intra-arterial systolic/diastolic blood pressure was 116 +/- 3/76 +/- 2 mmHg. Local indirect calorimetry indicated dominance of fat as the oxidative substrate (RQ 0.76 +/- 0.09) and an energy expenditure rate of 1.03 +/- 0.11 cal.min-1.dl-1 forearm vol. One hundred minutes of intra-arterial insulin infusion (deep venous plasma insulin concn of 125 +/- 11 microU/ml) had no detectable effect on forearm blood flow, resting forearm vascular resistance, heart rate, or blood pressure. Local hyperinsulinemia significantly stimulated glucose uptake (to 4.79 +/- 0.61 mumol.min-1.dl-1 forearm vol, P less than 0.001), lactate and pyruvate release (to 0.710 +/- 0.093 and 0.032 +/- 0.016 mumol.min-1.dl-1 forearm vol, respectively; P less than 0.01 for both), potassium uptake (0.76 +/- 0.22 mueq.min-1.dl-1, P less than 0.001), and free fatty acid uptake (0.123 +/- 0.041 mumol.min-1.dl-1 forearm vol, P less than 0.05); glycerol balance switched to a net uptake (P less than 0.001), alanine release was restrained by 33% (P less than 0.05), and beta-hydroxybutyrate and citrate release were unchanged. Despite these metabolic changes, local rates of substrate oxidation and energy expenditure were not altered by insulin. In contrast, forearm proton release was significantly stimulated by insulin (to 14.8 +/- 1.4 pmol.min-1.dl-1, P less than 0.02). Proton release was also found to be directly related to resting forearm vascular resistance independent of the effect of insulin (multiple r = 0.64, P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1990 Apr
PMID:Effects of insulin on hemodynamics and metabolism in human forearm. 218 Jul 59

It has been proposed that increased supply of gluconeogenic precursors may be largely responsible for the increased gluconeogenesis which contributes to fasting hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). Therefore, to test the hypothesis that an increase in gluconeogenic substrate supply per se could increase hepatic glucose output sufficiently to cause fasting hyperglycemia, we infused normal volunteers with sodium lactate at a rate approximately double the rate of appearance observed in NIDDM while clamping plasma insulin, glucagon, and growth hormone at basal levels. In control experiments, sodium bicarbonate was infused instead of sodium lactate at equimolar rates. In both experiments, [6-3H]-glucose was infused to measure glucose appearance and either [U-14C]lactate or [U-14C]alanine was infused to measure the rates of appearance and conversion of these substrates into plasma glucose. Plasma insulin, glucagon, growth hormone, C-peptide, and glycerol concentrations, and blood bicarbonate and pH in control and lactate infusion experiments were not significantly different. Infusion of lactate increased plasma lactate and alanine to 4.48 +/- 3 mM and 610 +/- 33 microM, respectively, from baseline values of 1.6 +/- 0.2 mM and 431 +/- 28 microM, both P less than 0.01; lactate and alanine rates of appearance increased to 38 +/- 1.0 and 8.0 +/- 0.3 mumol/kg per min (P less than 0.01 versus basal rates of 14.4 +/- 0.4 and 5.0 +/- 0.5 mumol/kg per min, respectively). With correction for Krebs cycle carbon exchange, lactate incorporation into plasma glucose increased nearly threefold to 10.4 mumol/kg per min and accounted for about 50% of overall glucose appearance. Alanine incorporation into plasma glucose increased more than twofold. Despite this marked increase in gluconeogenesis, neither overall hepatic glucose output nor plasma glucose increased and each was not significantly different from values observed in control experiments (10.8 +/- 0.5 vs. 10.8 +/- 0.5 mumol/kg per min and 5.4 +/- 0.4 vs. 5.3 +/- 0.3 mM, respectively). We, therefore, conclude that in normal humans there is an autoregulatory process independent of changes in plasma glucose and glucoregulatory hormone concentrations which prevents a substrate-induced increase in gluconeogenesis from increasing overall hepatic glucose output; since this process cannot be explained on the basis of inhibition of gluconeogenesis from other substrates, it probably involves diminution of glycogenolysis. A defect in this process could explain at least in part the increased hepatic glucose output found in NIDDM.
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PMID:Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans. Demonstration of hepatic autoregulation without a change in plasma glucose concentration. 220 Aug 5

The effects of CP 68722 (racemic englitazone) were examined in ob/ob mice, in adipocytes and soleus muscles from ob/ob mice, and in 3T3-L1 adipocytes. Administration of englitazone at 5-50 mg.kg-1.day-1 lowered plasma glucose and insulin dose dependently without producing frank hypoglycemia in either the diabetic or nondiabetic lean animals. The glucose-lowering effect in ob/ob mice preceded the reduction in hyperinsulinemia. On cessation of drug, plasma insulin returned to untreated levels within 48 h, whereas plasma glucose rose slowly over 5 days. Englitazone (50 mg/kg) for 11 days lowered plasma glucose (22.2 +/- 1.4 to 14.0 +/- 1.9 mM), insulin (7.57 +/- 0.67 to 1.64 +/- 0.60 nM), nonesterified fatty acids (1813 +/- 86 to 914 +/- 88 microM), glycerol (9.20 +/- 0.98 to 4.94 +/- 0.03 mM), triglycerides (1.99 +/- 0.25 to 1.03 +/- 0.11 g/L), and cholesterol (6.27 +/- 0.96 to 3.87 +/- 0.57 mM), but no effects were observed 3 h after a single dose. Basal and insulin-stimulated lipogenesis were enhanced in adipocytes from ob/ob mice treated with 50 mg/kg englitazone for 11 days compared with lipogenesis in cells from vehicle-treated controls. Treatment of ob/ob mice with 50 mg/kg englitazone reversed the defects in insulin-stimulated glycolysis (from [3-3H]glucose) and glycogenesis and basal glucose oxidation (from [1-14C]glucose) in isolated soleus muscles. Englitazone (30 microM) stimulated 2-deoxy-D-glucose transport in 3T3-L1 adipocytes from 0.37 +/- 0.03 to 0.65 +/- 0.06 and 1.53 nmol.min-1.mg-1 protein at 24 and 48 h, respectively. Thus, englitazone has 1) insulinomimetic and insulin-enhancing actions in vitro and 2) glucose-, insulin-, triglyceride-, and cholesterol-lowering properties in an animal model of non-insulin-dependent diabetes mellitus (NIDDM) in which sulfonylureas have little or no effect. Thus, this new agent may have beneficial effects including a reduced risk of hypoglycemia in patients with NIDDM.
Diabetes 1990 Oct
PMID:Actions of novel antidiabetic agent englitazone in hyperglycemic hyperinsulinemic ob/ob mice. 221 74


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