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

The receptor binding characteristics and biologic protency of biosynthetic human proinsulin (rDNA) were determined in isolated rat adipocytes and compared with those of insulin. In competition with 125I(A14)-iodoinsulin for binding to adipocyte receptors at 15 degrees C, proinsulin showed a 100-fold lower affinity for binding than did insulin. A proinsulin concentration of 3.2 +/- 0.8 X 10(-7) M was required for 50% inhibition of tracer binding as compared with a concentration of 1.7 +/- 0.3 X 10(-9) M for insulin. These results were confirmed in direct competition studies using proinsulin and 125I-iodoproinsulin. A similar 100-fold difference was also observed in competitive binding experiments conducted at 37 degrees C. The biologic potency of human proinsulin was evaluated by its ability to stimulate glucose incorporation into total fat cell lipid and also by its antilipolytic activity. Glucose incorporation into lipid was half-maximal at a proinsulin concentration of 1.5 +/- 0.4 X 10(-8) M, whereas the same response was observed at an insulin concentration of 5.2 +/- 1 X 10(-11) M. Proinsulin also demonstrated an antilipolytic potency that was less than 1% that of insulin. The time course over which insulin and proinsulin stimulated glucose incorporation into lipid was the same, as was the time course over which the stimulation dissipated after removal of the hormones. No synergism of insulin and proinsulin stimulation of lipogenesis was observed when fat cells were incubated with submaximal concentrations of the two hormones.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Nov
PMID:In vitro activity of biosynthetic human proinsulin. Receptor binding and biologic potency of proinsulin and insulin in isolated rat adipocytes. 638 25

We have used two methods for the preparation of a highly homogeneous insulin with high specific activity. After iodination with chloramine T, the labeled peptides were retained on a disposable Sep Pak cartridge and subsequently eluted. The eluted labeled insulins were further purified by either DEAE cellulose or high performance liquid chromatography (HPLC) to separate A14-125I- from A19-125I-insulin. Both methods of chromatography were effective, but HPLC offered the advantage of better resolution in less time and higher yields of A14-125I-insulin, which is suitable for biologic studies in various target tissues.
Diabetes 1982 Dec
PMID:A rapid means of separating A14-125I-insulin from heterogeneously labeled insulin molecules for biologic studies. 675 25

The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono-125I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis.
Diabetes 1982 Oct
PMID:Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus. 675 24

To assess whether human insulin (recombinant DNA) is superior to porcine insulin, we compared the biologic effect of these two insulin preparations on rat and human adipocyte lipogenesis in vitro. The biologic potency of these two insulin preparations was similar on both human and rat adipocytes. Iodination of human and porcine insulin with 125I at A14 position led to a significant but similar loss of potency of both insulin preparations.
Diabetes Care
PMID:Comparison of biologic potency of human insulin (recombinant DNA) and purified porcine insulin (PPI) on the rat and human adipocyte lipogenesis model. 676 17

Some immunologic properties of biosynthetic human insulin (BHI) were examined in vitro. An identical behavior was found for BHI and pancreatic human insulin as standard preparation and for A14-mono-labeled BHI and pork insulin as tracer in the insulin radioimmunoassay. BHI proved to be free of human proinsulin and C-peptide. Insulin antibodies in serum of two diabetic patients showed a preferential binding of 125I-bovine insulin. However, the antibody titers were almost identical for A14-mono-labeled BHI and pork insulin. These studies did not reveal any characteristic immunologic properties of BHI compared with highly purified pancreatic human and pork insulin.
Diabetes Care
PMID:Immunologic properties of biosynthetic human insulin in vitro. 701 27

Biosynthetic human insulin (BHI) and pancreatic human insulin were compared with respect to receptor binding in a heterologous assay system: displacement of pork A14-125I-monoiodoinsulin from receptors on pig hepatocytes. The concentrations of human insulin giving half-maximal displacement were identical for both preparations, i.e., 0.5 nM. Their relative potency was 1.01 +/- 0.14 (SD, N = 5), suggesting that biosynthetic and pancreatic human insulin exert the same biologic activity.
Diabetes Care
PMID:Receptor binding of biosynthetic human insulin on isolated pig hepatocytes. 701 34

The biologic potency (plasma glucose depression) of pancreatic human insulin was compared with that of biosynthetic human insulin (BHI), manufactured by recombinant DNA techniques in bacteria, following intravenous injection in rats. The specific activity of the pancreatic human insulin was 32 U/mg, while that for BHI was 27 U/mg. These values were not significantly difference, but were higher than the value for pancreatic pork insulin (25 U/mg). The pharmacokinetics of i.v. injected A14-mono-125I-insulin (pork) were found to be similar to those observed for semisynthetic [3H]insulin (pork), the respective metabolic clearance rates (MCR) being 20.8 +/- 0.8 ml/min/kg (N = 4) and 23.6 +/- 1 ml/min/kg (N = 5) (P greater than 0.1). The MCR for A14-mono-125I-BHI was 24.6 +/- 2.2 ml/min/kg (N = 4), which was significantly higher (P less than 0.025) than the value for A14-mono-125I-pork insulin. BHI is thus no less active than pork insulin in rats and possibly somewhat more active. The small difference in activity may be due to increased affinity for rat insulin receptors, resulting in a more rapid MCR for BHI. In addition, the A14-monoiodinated insulin tracer used in these studies is indistinguishable from semisynthetic [3H]insulin in terms of its rate of clearance, indicating that the insulin molecule has not suffered any iodination damage and is thus a valid tracer for metabolic and receptor studies.
Diabetes Care
PMID:Biologic activity and pharmacokinetics of biosynthetic human insulin in the rat. 701 35

125I-insulin was prepared by reacting 17.4 nmol porcine insulin (100 micrograms) with 5 mCi 125I (about 2.4 nmol) using the lactoperoxidase method. The reaction product was subjected to gel electrophoresis and the band containing A14 [125I]monoiodoinsulin was eluted. This preparation showed a specific activity of about 1.5 Ci/mumol as evaluated by radioimmunoassay and bioassay, i.e., about 75% of the theoretical maximum. The content of radioactive derivatives other than A14 monoiodoinsulin was less than 2%. The binding affinity of tracer A14 monoiodoinsulin to adipocytes, hepatocytes, and cultured human lymphocytes was twice as high as that of A19 monoiodoinsulin. Binding to antibodies was examined to 10 guinea pig anti-insulin sera. Three sera did not distinguish between the two tracers, whereas seven exhibited higher binding of the A14 tracer. A detailed analysis of one of the discriminating sera showed that the average affinity constant was about 2.5 times lower for the A19 tracer than for the A14 tracer. The A14 monoiodoinsulin tracer is remarkably stable. After 200 days the specific activity had declined to about half of its original value which is consistent with the hypothesis that the physical decay of [125I]monoiodoinsulin (T 1/2 equals 60 days) extinguishes the activity of the molecule without causing major damage of other molecules. By this time 96% of the radioactivity migrated with insulin when subjected to gel filtration on Sephadex G-50, 4% was in the void volume, and nothing in the total column volume or later. Binding to receptors was indistinguishable from that obtained at time zero. It is concluded that Tyr A14[125I]monoiodoinsulin represents an advance in biologic work as compared with previous tracers for insulin.
Diabetes 1981 Jan
PMID:Tyrosine A14[125I]monoiodoinsulin: Preparation, Biologic Properties, and long-term stability. 701 99

Patients with insulin-dependent diabetes who receive pancreas/kidney transplants lose their need for insulin injections, but they become hyperinsulinemic and insulin resistant, and sometimes develop noninsulin-dependent diabetes mellitus. The reason for the insulin resistance is not well understood. Specifically, it is not known whether they become resistant to the action of insulin on lipid metabolism. Euglycemic-hyperinsulinemic clamps were performed in six pancreas/kidney (P/K) recipients, six kidney (K) recipients (to control for immunosuppressive therapy), and eight healthy controls. Measured were leg blood flow (by plethysmography), rates of lipolysis (with [2H5] glycerol), fatty acid oxidation (by indirect calorimetry), fatty acid reesterification (with [2H5]glycerol and [1-13C]palmitate), monocyte membrane insulin binding (with [125I]Tyr-A14 insulin), and insulin receptor mass (by RIA). Fasting plasma insulin concentrations were 2 times higher in P/K and K recipients (108 pmol/L) than in controls (54 pmol/L). Insulin receptor mass in solubilized monocyte membranes from P/K and K recipients was reduced by 61% and 63%, respectively, whereas insulin binding was reduced by 73% and 70%, respectively. P/K and K recipients were resistant to the inhibitory action of insulin on lipolysis (P/K vs. controls, P < 0.01; K vs. controls, P < 0.02) and on fatty acid reesterification (P/K vs. controls, P < 0.02; K vs. controls, P < 0.03). P/K recipients appeared to be more resistant than K recipients, but the differences between the two groups were not statistically significant. We conclude that P/K recipients were hyperinsulinemic, had down-regulated the number of their monocyte insulin receptors, and were resistant to the antilipolytic action of insulin.
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PMID:Insulin receptor down-regulation and impaired antilipolytic action of insulin in diabetic patients after pancreas/kidney transplantation. 812 38

We have previously shown that the glucose intolerance and the hyperglycemic state in the GK rat, a new spontaneous model of non-insulin-dependent (type II) diabetes without obesity, are partly accounted for by an alteration of the pancreatic B cell response. On the other hand, the hyperglycemic-hyperinsulinemic pattern in these rats suggests a decrease of response to insulin in the basal state. In the present study, in vivo insulin action was assessed in 8-wk-old GK females at basal and submaximal (euglycemic clamp) insulin levels. Overall glucose utilization (OGU), individual tissue glucose utilization (ITGU, in vivo uptake of the glucose analogue 2-deoxy-D-glucose as the relative index of glucose metabolism), as well as hepatic glucose production (GP) and liver insulin receptor properties were determined under these two conditions. The basal OGU was significantly higher in the GK females, compared with that in control Wistar females. The hyperinsulinemic-euglycemic clamp experiments indicated that peripheral insulin resistance was installed at 8 wk of age in the GK females because 1) OGU was significantly lower and 2) in some peripheral tissues (epitrochlearis muscle, periovarian, and inguinal white adipose tissues), but not all, ITGU was significantly lower compared with corresponding ITGU in control rats. In the basal state GP was significantly higher in the GK rats. At submaximal hyperinsulinemia (and euglycemia), it was less effectively suppressed than in the controls, thus demonstrating liver insulin resistance. Under both basal state and clamp condition, binding of 125I-A14-insulin to liver membranes of GK rats was significantly decreased by 20-30%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin resistance in the GK rat: decreased receptor number but normal kinase activity in liver. 823 7


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