Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether prolonged nicotinic acid (NA) administration produces insulin resistance and, if so, how the normal pancreatic islet adapts to prolonged insulin resistance, we administered incremental doses of NA to 11 normal men for 2 wk, ending at 2 g/day. Insulin sensitivity was measured with Bergman's minimal model. Islet function was evaluated by measurement of acute insulin (AIR) and glucagon (AGR) responses to arginine at three glucose levels. Insulin resistance was demonstrated and quantified by a marked drop in the insulin sensitivity index (Sl) from 6.72 +/- 0.77 to 2.47 +/- 0.36 x 10(-5) min-1/pM (P less than .0001) and resulted in a doubling of basal immunoreactive insulin levels (from 75 +/- 7 to 157 +/- 21 pM, P less than .001) with no change in fasting glucose (5.5 +/- 0.1 vs. 5.7 +/- 0.1 mM). Proinsulin levels also increased (from 9 +/- 1 to 15 +/- 2 pM, P less than .005), but the ratio of proinsulin to immunoreactive insulin did not change (12.7 +/- 1.9 vs. 10.3 +/- 1.9%). beta-Cell changes were characterized by increases in the AIR to glucose (from 548 +/- 157 to 829 +/- 157 pM, P less than .005) and in the AIR to arginine at the fasting glucose level (from 431 +/- 54 to 788 +/- 164 pM, P less than .05). At the maximal hyperglycemia level the AIR to arginine represents beta-cell secretory capacity, and this increased with administration of NA (from 2062 +/- 267 to 2630 +/- 363 pM, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 May
PMID:Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. 265 28

During the preclinical period of human insulin-dependent diabetes, both impaired pancreatic beta-cell function and increased insulin resistance are found, although normoglycemia is preserved. To better understand the changes in beta-cell function and insulin sensitivity that occur in preclinical insulin-dependent diabetes, we performed a panel of in vivo beta-cell function tests and measured insulin sensitivity in adolescent male baboons both in normal health and after a small dose of streptozocin which did not induce hyperglycemia. Nine animals were studied before (stage 1) and 1 week after receiving a low dose of streptozocin (stage 2). There was no change in fasting plasma glucose or insulin. The mean glucose disposal rate (Kg) remained within the normal range, but dropped from 2.0 +/- 0.2% +/- SE) to 1.2 +/- 0.1%/min (P less than 0.01), the acute insulin response to arginine (AIR(arg)) fell from 67.7 +/- 19.4 microU/mL (485.8 +/- 139.2 pmol/L) to 32.8 +/- 7.2 microU/mL (235.3 +/- 51.7 pmol/L; P less than 0.05), and the acute insulin response to glucose (AIR(gluc)) fell from 881 +/- 243 microU/mL.10 min (6321 +/- 1744 pmol/L.10 min) to 334 +/- 82 microU/mL.10 min (2396 +/- 588 pmol/L.10 min; P less than 0.01). The most dramatic change, however, was in the ability of hyperglycemia to potentiate AIR(arg) (expressed as the slope of potentiation). This was reduced by 94% from 1.8 +/- 0.5 to 0.1 +/- 0.1 (P less than 0.01), with almost no overlap in values between stages 1 and 2. Insulin sensitivity was also lower 1 week after streptozocin treatment. When the animals were restudied 8 weeks after streptozocin treatment (stage 3) most measures of beta-cell function were not significantly different from those in stage 1. The fasting plasma glucose level was 85.4 +/- 4.3 mg/dL (4.7 +/- 0.2 mmol/L), Kg was 1.8 +/- 0.3%/min, fasting plasma insulin was 35.9 +/- 8.5 microU/mL (257.6 +/- 61.0 pmol/L), AIR(arg) was 67.0 +/- 15.4 microU/mL (480.7 +/- 110.5 pmol/L), and AIR(gluc) was 615.3 +/- 265.3 microU/mL.10 min (4413 +/- 1901 pmol/L.10 min), and tissue insulin sensitivity was 2.7 +/- 0.4 x 10(4) min/microU.mL. These values show extensive overlap with those of stage 1, from which they are not significantly different. The slope of glucose potentiation, however, remained low in all animals at stage 3.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Defects in beta-cell function and insulin sensitivity in normoglycemic streptozocin-treated baboons: a model of preclinical insulin-dependent diabetes. 304 63

Both rat alveolar macrophages and a human macrophages cell line with characteristics of human tissue (e.g., alveolar) macrophages (THP-1) were found to inhibit the germination of Rhizopus spores. However, the conditions under which fungistatic activity occurs are different for these two cell types. The inhibition of Rhizopus spore germination by rat alveolar macrophages requires the activation of macrophages and the presence of serum and L-arginine. During rat alveolar macrophage-mediated fungistatic activity, L-arginine is oxidized to nitric. Human macrophage-mediated fungistatic activity is similar to that mediated by rat macrophages in terms of the serum requirement, but it does not require L-arginine. Human macrophages did not produce any nitrite detectable by the colorimetric assay. Their ability to inhibit germination was enhanced by the combination of endotoxin and gamma interferon. The inhibition of Rhizopus spore germination by rat alveolar macrophages is thus mediated by the generation of nitric oxide, whereas the mechanism of similar inhibition by human macrophages remains poorly understood. Serum samples from diabetic rats as well as from patients with diabetes or uremia decreased the inhibitory effect of macrophages on spore germination. Dialysis of the serum samples against a buffered salt solution antagonized this phenomenon, indicating that a low-molecular-weight factor in the sera of patients with diabetes or uremia may modulate local antifungal defense mechanisms. The absence of L-arginine-dependent nitrogen oxidation in human macrophages, compared with its presence in rat alveolar macrophages, under conditions during which fungistatic activity occurs suggests that this phenomenon is species specific.
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PMID:Human and rat macrophages mediate fungistatic activity against Rhizopus species differently: in vitro and ex vivo studies. 759 Oct 90

Insulin and glucagon secretion was compared in women with impaired glucose tolerance (IGT; n = 19, age 58.4 +/- 0.3 yr; mean +/- SD) and women with normal glucose tolerance (NGT; n = 40, age 58.4 +/- 0.3 yr). Fasting plasma insulin levels were higher in IGT than in NGT (P = 0.026), whereas fasting glucose and glucagon levels were not different. Arginine was injected intravenously (5 g), which rapidly stimulated insulin and glucagon secretion in all subjects. Raising the blood glucose (BG) to 14 and 28 mmol/L potentiated insulin secretion and inhibited glucagon secretion. The acute insulin response to arginine (AIR = 2-5 min postload increase) at BG 14 mmol/L, but not at fasting BG or BG 28 mmol/L, was lower in IGT than in NGT (P = 0.033), as was the glucose potentiation of AIR (slopeAIR) (P = 0.020). The acute glucagon response (AGR) was higher in IGT than in NGT at BG 14 mmol/L (P = 0.016). SlopeAGR (glucose inhibition of AGR) was reduced in IGT (P = 0.001). In NGT, there was a significant inverse correlation between slopeAIR and slopeAGR (P = 0.002) not seen in IGT. We conclude that in IGT with normal fasting BG, the glucose modulation of islet function is impaired, indicating that islet dysfunction is an early lesion during the development of noninsulin-dependent diabetes mellitus.
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PMID:Glucose modulation of insulin and glucagon secretion is altered in impaired glucose tolerance. 777 22

The risk of cardiovascular disease is increased in subjects with insulin-dependent diabetes mellitus (IDDM), although the mechanism remains unclear. To assess whether diabetic postprandial triglyceride (TG)-rich lipoprotein (TGRLP) subfractions (Sf > 400, 100-400, and 20-100) isolated from non-obese, normolipidemic IDDM subjects (n = 14) are potentially more atherogenic than lipoproteins from normal controls (n = 13), we measured cholesteryl ester (CE) synthesis and esterified cholesterol (EC) mass accumulation in THP-1 macrophages incubated with postprandial TGRLP. Diabetic Sf > 400 and Sf 100-400 but not Sf 20-100 significantly increased the mean (+/- SE) rate (pmol/mg cell protein/24 h) of CE synthesis in THP-1 macrophages compared with normal controls (Sf > 400, 673 +/- 26 v 301 +/- 64, P < .025; Sf 100-400, 560 +/- 27 v 298 +/- 39, P < .0005; Sf 20-100, 743 +/- 51 v 831 +/- 45). As well, all three diabetic TGRLP increased the mass of EC (microgram EC/mg cell protein/48 h) as compared with normal controls (Sf > 400, 4.9 +/- 0.61 v 2.9 +/- 0.50, P < .025; Sf 100-400, 5.7 +/- 0.91 v 3.4 +/- 0.34, P < .05; Sf 20-100, 5.4 +/- 0.7 v 3.2 +/- 0.52, P < .05). This effect is sustained for at least 7 hours postprandially and is greater than that of fasting Sf 100-400 (P < .03) and Sf 20-100 (P < .05) and similar to malondealdehyde low-density lipoprotein (MDA-LDL). To assess the mechanisms involved, the chemical composition and cellular degradation of diabetic and control lipoproteins were compared. Postprandial diabetic Sf 100-400 had abnormal composition (phospholipid to protein ratio, 1.86 +/- 0.14 v 1.5 +/- 0.13, P < .05) and in preliminary experiments demonstrated increased cell association (mean +/- SD at 6 hours, 126 +/- 34.3 v 57 +/- 4.2) and degradation (584 +/- 141 v 254 +/- 13) compared with that of normal controls, and may account for the observed increase in EC accumulation. In summary, postprandial diabetic Sf > 400 and Sf 100-400 TGRLP increase CE synthesis and Sf > 400, Sf 100-400, and Sf 20-100 lipoproteins increase EC accumulation in human macrophages compared with normal control lipoproteins. Diabetic Sf 100-400 lipoproteins have abnormal composition and seem to have increased cellular association and degradation compared with normal lipoproteins. Our findings suggest a role for postprandial TGRLP in the increased risk of cardiovascular disease among subjects with IDDM.
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PMID:Diabetic postprandial triglyceride-rich lipoproteins increase esterified cholesterol accumulation in THP-1 macrophages. 808 80

This study was designed to define the effects on glucose metabolism of small increases of plasma EPI, comparable to increases observed during physiological sympathoadrenal activation. This study was also designed to determine the effects of EPI on glucose metabolism in older adults, in whom changes in adrenergic responsiveness of several tissues were described. Tolbutamide-boosted IVGTTs were performed during intravenous infusions of saline (control) or EPI at 2.7, 5.5, and 10.9 mmol/min to achieve physiological levels of EPI in 7 young subjects (19-26 yr of age) and 7 old subjects (62-75 yr of age), all with a normal screening OGTT. IVGTT results were analyzed to determine the AIR and with the minimal model method of Bergman to determine SI and SG. A significant fall was observed in AIR, SI, and SG for all subjects, even with the lowest dose of EPI, which resulted in only a two- to threefold increase in plasma EPI. Older subjects had a delayed recovery from hyperglycemia during the EPI infusions, although we detected no significant differences between the young and old subjects in the ability of EPI to alter either acute phase insulin secretion or insulin action. In contrast, the impairment of SG by EPI appeared to be greater in the elderly. We conclude that small increases of plasma EPI can significantly affect determinants of glucose tolerance in both young and old people.
Diabetes 1993 Feb
PMID:Effects of epinephrine on insulin secretion and action in humans. Interaction with aging. 842 66

The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics. the greater insulin resistance may be due to greater adiposity and other behavioral factors.
Diabetes 1996 Jun
PMID:Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study. 863 47

To clarify the etiology of accelerated atherosclerosis in patients with diabetes mellitus, we measured expression of intercellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), and E-selection on the cell surface by enzyme-linked immunosorbent assay and ICAM-1 mRNA content in human umbilical vein endothelial cells exposed to 5.5 mM glucose (NG), 33 mM glucose (HG), or 27.5 mM mannitol plus 5.5 mM glucose (HM).1) Cell-surface ICAM-1 expression in HG and HM cells was maximally increased by 37% and 32% (P < 0.01), respectively. This effect was dependent on glucose concentration in the medium and was found as early as 24 h and maintained until 6 days after exposing cells of HG. However, neither VCAM-1 nor E-selection expression were affected by HG conditions. 2) Both HG and HM induced increased mRNA content between 6 and 12 h after the stimulation. 3) Adhesion of THP-1 cells to endothelial cells exposed to HG and HM was increased, when compared to NG conditions. These results indicate that osmotic effects can induce increased mRNA and cell-surface expression of ICAM-1 via an as yet unknown mechanism.
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PMID:Expression of intercellular adhesion molecules 1 (ICAM-1) via an osmotic effect in human umbilical vein endothelial cells exposed to high glucose medium. 863 95

Human serum albumin modified with 1-2 methylglyoxal residues per molecule of protein (MGmin-HSA) stimulated the synthesis and secretion of interleukin 1 beta (IL-1 beta) from human monocytic THP-1 cells in vitro. It was a more potent inducer of IL-1 beta synthesis than human serum albumin highly-modified with glucose-derived advanced glycation endproducts (AGE-HSA). With 20 microM ligand. IL-1 beta synthesis was (pg/10(6) cells): MGmin-HSA 484.5 +/- 50.3; AGE-HSA 30.6 +/- 2.0 (n = 3). IL-1 beta synthesis increased markedly with MGmin-HSA concentrations > 5 microM. IL-1 beta synthesis and secretion from monocytes in response to methylglyoxal-modified proteins in vivo may contribute to the development of macro- and micro-angiopathy, particularly in diabetes mellitus.
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PMID:Induction of synthesis and secretion of interleukin 1 beta in the human monocytic THP-1 cells by human serum albumins modified with methylglyoxal and advanced glycation endproducts. 879 54

The aim of the present study was to estimate insulin secretion, insulin sensitivity (SI), and glucose effectiveness at basal insulin (SG) in subjects with bulimia nervosa. Eight bulimic patients and eight age-, body mass index-, and sex-matched healthy control subjects without a family history of diabetes were studied. The subjects all had normal glucose tolerance. They underwent a modified frequently sampled intravenous glucose tolerance test; glucose (300 mg/kg body weight) was administered, and insulin (4 mU/kg body weight/min) was infused from 20 to 25 minutes after administration of glucose. SI and SG were estimated by Bergman's minimal model method. Basal insulin (27 +/- 3 v 45 +/- 3 pmol/L) was significantly lower in bulimic patients than in normal controls (P < .05), but basal glucose was similar between the two groups (4.5 +/- 0.1 v 4.9 +/- 0.1 mmol/L, P > .05). The glucose disappearance rate (KG) and acute insulin response to glucose estimated by the intravenous glucose tolerance test (AIR(glucose)) were similar between the two groups (KG, 1.35 +/- 0.29 v 2.20 +/- 0.21 min(-1), P > .05; AIR(glucose), 2,920 +/- 547 v 2,368 +/- 367 pmol/L x min, P > .05). No significant difference was observed in SI between the two groups (1.34 +/- 0.18 v 1.25 +/- 0.20 x 10(-4) x min(-1) x pmol/L(-1), P > .05). On the other hand, glucose effectiveness at basal (SG) and zero (GEZI) insulin was significantly diminished in comparison to normal controls (SG, 0.011 +/- 0.002 v 0.024 +/- 0.002 min(-1), P < .01; GEZI, 0.008 +/- 0.002 v 0.017 +/- 0.003 min(-1), P < .01). Thus, bulimic patients with normal glucose tolerance without a family history of diabetes were characterized by normal insulin secretion, normal SI, and reduced SG and GEZI.
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PMID:Intravenous glucose tolerance test-derived glucose effectiveness in bulimia nervosa. 916 Aug 11


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