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

Tissue sensitivity to insulin was studied using the euglycemic insulin clamp technique (delta plasma insulin above basal 90 microU/ml) in eight patients with type I diabetes mellitus (IDDM) before and after 4-8 mo of continuous subcutaneous insulin infusion (CSII) and in 36 age-matched control subjects. Institution of CSII was associated with significant improvements in glycosylated hemoglobin (HbA1) (11.2 +/- 0.6% versus 8.1 +/- 0.4%; P less than 0.001) and mean 24-h plasma glucose concentrations (239 +/- 23 mg/dl versus 106 +/- 18 mg/dl; P less than 0.001). Insulin-mediated glucose metabolism in the diabetic patients pre-CSII (3.92 +/- 0.36 mg/kg X min) was reduced by 44% compared with controls (7.03 +/- 0.22 mg/kg X min; P less than 0.001). After 4-8 mo of improved glycemic control, improved tissue sensitivity to insulin was observed (5.33 +/- 0.75 mg/kg X min; P less than 0.05 versus pre-CSII). However, insulin-mediated glucose utilization still remained significantly below control values (P less than 0.01). During hyperinsulinemia, hepatic glucose production (3-3H-glucose) was suppressed by over 90% in diabetic patients (pre- and post-CSII) and in control subjects. We conclude that near-normalization of glucose metabolism with CSII partially corrects, but does not restore to normal, insulin-stimulated glucose uptake in IDDM. Our failure to totally reverse the impaired response of peripheral tissues to insulin in IDDM patients may be attributed to inadequate metabolic correction, the peripheral route of insulin administration, or a primary defect in glucose metabolism.
Diabetes 1985 Aug
PMID:Improved insulin sensitivity in patients with type I diabetes mellitus after CSII. 389 30

Glucose intolerance is a common concomitant of untreated chronic renal failure, but the effect of long-term treatment on the insulin resistance believed to be behind it is as yet not clarified. Peripheral tissue sensitivity to insulin was therefore examined in 7 dialyzed uraemic patients, 8 undialyzed uraemic and 8 matched healthy subjects using the hyperinsulinaemic euglycaemic clamp technique. The dialyzed subjects had been on maintenance haemodialysis for a mean of 4 yr (range, 3-131 months) and were studied both before and after a single random dialysis. The clamping was performed during 150 min using a glucose controlled insulin infusion system (Biostator). Insulin was infused at a rate of 2.0 mU/kg/min. Tissue sensitivity to insulin was expressed as glucose uptake (M) at steady state (90-150 min) over steady state serum insulin concentration (I). While M was significantly greater in healthy subjects (12.52 +/- 1.02 mg/kg/min, mean +/- 1 SEM) than in dialyzed uraemics (9.59 +/- 0.78 mg/kg/min and 9.36 +/- 0.70 mg/kg/min, both p less than 0.05), M/I was similar in chronically dialyzed patients (before and after dialysis: 0.098 +/- 0.017 mg/kg/min per microU/ml vs 0.104 +/- 0.020 mg/kg/min per microU/ml) and in controls (0.111 +/- 0.015 mg/kg/min per microU/ml; p greater than 0.20). In contrast M/I ratio of uraemic subjects who had never been dialyzed (0.062 +/- mg/kg/min per microU/ml) was significantly reduced (both p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1985 Mar
PMID:Assessment of tissue sensitivity to insulin in uraemic patients on long-term haemodialysis therapy. 404 32

Pancreatogenic diabetes (PD), secondary either to chronic calcific pancreatitis or to pancreatectomy, is characterized by higher frequency of hypoglycemic events during insulin therapy in comparison with type I insulin-dependent diabetes (IDD). Not only glucagon deficiency, but an enhanced peripheral tissue sensitivity to insulin could account for this metabolic behavior. We investigated several facets of insulin action, e.g., tissue sensitivity to insulin, insulin binding to red cells, and insulin kinetics in seven patients with PD in comparison with type I. Tissue sensitivity to insulin was evaluated by means of the glucose-insulin clamp technique as M/I x 100 ratio (mg . kg .-1 min-1/muU . ml-1), where M is the amount of glucose infused by Biostator GCIIS to clamp BG at basal level and I is the free insulin plateau concentration achieved by a primed-constant insulin infusion. At high BG 15 h after the last injection of regular insulin M/I x 100 was 7.79 (range 4.25-9.75) in PD and 4.20 (range 1.20-6.91) in D (P less than 0.05). At low and equal BG M/I x 100 was 8.55 (range 6.35-9.72) in PD and 3.42 (range 1.19-6.75) in D (P less than 0.01). The rate of endogenous glucose production was nearly totally suppressed in both groups of patients. Just before the two clamps, 125I-insulin specific binding to red cells was studied. The maximum specific binding was significantly higher in PD than in D at high BG (10.7 +/- 1.7 vs. 7.4 +/- 0.8/10(9) red cells) and at low and equal BG (12.4 +/- 1.2 vs. 6.8 +/- 0.8). Receptor concentration also was significantly higher in PD thant in D (P less than 0.02) while no significant differences were found in high affinity (Ke). Insulin kinetic data were analysed by using both "Model independent" (or noncompartmental) method and compartmental modeling. Patients with PD had significantly higher (P less than 0.05) plasma clearance of insulin.
Diabetes 1982 Apr
PMID:Insulin sensitivity, binding, and kinetics in pancreatogenic and type I diabetes. 675 50

The therapeutic efficacy of human insulin (recombinant DNA) was compared with that of purified porcine insulin (PPI) in seven male subjects with previously treated insulin-dependent diabetes mellitus. In a random crossover design the patients received either PPI or human insulin during one of two consecutive 7-day periods of intensive insulin therapy. Control was evaluated on days 6 and 13. Tissue sensitivity and responsiveness to the study insulins were determined by insulin dose-response studies performed using the euglycemic glucose clamp on days 7 and 14. Insulin dose and all measures of control on days 6 and 13 were not statistically different between treatments. When the insulin dose-response studies during each treatment were compared there were no differences between them. Thus, in previously treated patients with insulin-dependent diabetes, undergoing brief but intensive insulin therapy with continuous subcutaneous insulin infusion, human insulin is as clinically efficacious as PPI. Furthermore, insulin sensitivity and responsiveness, as assessed by dose-response studies during the euglycemic glucose clamp were equivalent for both insulins.
Diabetes Care
PMID:The therapeutic efficacy of human insulin (recombinant DNA) in patients with insulin-dependent diabetes mellitus: a comparative study with purified porcine insulin. 676 46

Altered glucocorticoid hormone action may contribute to the etiology of the metabolic syndrome, but the molecular mechanisms are poorly defined. Tissue sensitivity to glucocorticoid is regulated by expression of the glucocorticoid receptor (GR)-alpha and 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1)-mediated intracellular synthesis of active cortisol from inactive cortisone. We have analyzed GRalpha and 11beta-HSD1 expression in skeletal myoblasts from men (n = 14) with contrasting levels of insulin sensitivity (euglycemic clamp measurements of insulin-dependent glucose disposal rate), blood pressure, and adiposity. Positive associations were evident between myoblast expression of GRalpha under basal conditions and levels of insulin resistance (r(2) = 0.34, P < 0.05), BMI (r(2) = 0.49, P < 0.01), percent body fat (r(2) = 0.34, P < 0.02), and blood pressure (r(2) = 0.86, P < 0.001). Similar associations were evident when myoblasts were incubated with physiological levels of cortisol (P < 0.01 for all). Importantly, GRalpha expression was unaffected by variations in in vivo concentrations of insulin, IGF-1, or glucose concentrations. In common with the GR, 11beta-HSD1 expression in myoblasts incubated with physiological concentrations of cortisol in vitro was positively associated with levels of insulin resistance (r(2) = 0.68, P < 0.001), BMI (r(2) = 0.63, P < 0.005), and blood pressure (r(2) = 0.27, P < 0.05). Regulation of GRalpha and 11beta-HSD1 by cortisol was abolished by the GR antagonist RU38486. In summary, our data suggest that raised skeletal muscle cell expression of GRalpha and 11beta -HSD1-mediated regulation of intracellular cortisol may play a fundamental role in mechanisms contributing to the pathogenesis of the metabolic syndrome.
Diabetes 2002 Apr
PMID:Increased glucocorticoid receptor expression in human skeletal muscle cells may contribute to the pathogenesis of the metabolic syndrome. 1191 27

In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species.
Diabetes 2016 04
PMID:Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice. 2674 Jun 2