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

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

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

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

Numerous factors impinge on beta-cell function, and include the genetic background and insulin sensitivity of the individual. The aim of the present study was to evaluate the impact of a family history of non-insulin-dependent diabetes mellitus (NIDDM) on beta-cell function and to determine whether the relationships between beta-cell function and insulin sensitivity and age are influenced by a family history of diabetes. Thirty-three healthy control subjects (CON), 20 normal glucose-tolerant first-degree relatives of known NIDDM patients (REL), and 12 nondiabetic identical twins with an identical twin with known NIDDM were studied. Insulin and C-peptide responses to an acute intravenous glucose (AIRg) and glucagon bolus (at euglycemia [AIR[G.GON]]) were measured, as well as each individual's insulin sensitivity. Fasting insulin and C-peptide levels were similar in all groups. AIRg was significantly reduced by 65% in the nondiabetic twins compared with the CON and REL groups, with the latter group being similar to CON, whereas for the AIR[G.GON], the insulin responses in the twin subjects were reduced only by 35% compared with CON. Following stepwise (default) multiple regression analysis, three independent variables (insulin sensitivity, 23%; family history of NIDDM, 20%; and fasting glucose, 7%) were identified, and these combined to fit a model for prediction of acute beta-cell responses to glucose that yielded an R2 (adjusted) value of 50%. Following analysis of covariance (ANCOVA), a positive family history of NIDDM and insulin sensitivity but not the age of the subject were confirmed as separate factors affecting AIRg. In conclusion, in subjects with normal or mild glucose intolerance, the individual's genetic background and insulin sensitivity are important determinants of insulin secretion.
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PMID:Impact of family history of diabetes on the assessment of beta-cell function. 959 41

A total of 85 islet cell antibody (ICA)+ or insulin autoantibody (IAA)+ relatives of patients with type 1 diabetes have been followed as part of the Seattle Family Study for a mean of 2.8 years. Of the subjects followed, 10 developed diabetes during this time period. The presence of GAD antibodies was strongly associated with the development of diabetes. In contrast, the presence of IAAs did not influence the risk of diabetes among ICA+ GAD+ subjects. When either the initial absolute acute insulin response to glucose (AIRg) or the AIR percentile, which accounts for the individual's insulin sensitivity, was below the 10th percentile of normal subjects, the risk of diabetes approached 50% at 5 years. However, impaired beta-cell function did not influence the risk of diabetes among those who were GAD+. There were 13 subjects with low AIRg and 13 subjects with two or more antibodies who had not progressed to diabetes during the course of the study. Other measurements of beta-cell function or demographic characteristics were not different in this group of nonprogressors compared with those with low AIRg who did not progress to diabetes. We conclude that ICA+ relatives with GAD antibodies or low AIRg have a high risk for development of diabetes, but among ICA+ GAD+ relatives, the addition of IAA or a single determination of AIRg does not enhance the prediction of diabetes. We suggest that prediction of diabetes risk depends on both the type and the number of antibodies present. In addition, there are a group of ICA+ relatives with low AIRg and/or multiple antibodies who have not progressed to diabetes over the course of the study.
Diabetes 1999 Jan
PMID:Relationship of beta-cell function and autoantibodies to progression and nonprogression of subclinical type 1 diabetes: follow-up of the Seattle Family Study. 989 39

Proinsulin release is increased relative to insulin secretion in subjects with type 2 diabetes, indicative of islet dysfunction. However, it has not been conclusively shown whether there is an increased relative proinsulin release in subjects with impaired glucose tolerance (IGT), i.e. whether it precedes the development of diabetes. We therefore determined the proinsulin to insulin ratios in the fasting state and after acute stimulation of insulin secretion in 23 postmenopausal women, aged 61-62 yr (mean +/- SD, 61.7 +/- 0.5 yr). Ten women had normal glucose tolerance (NGT), and 13 had IGT. The groups were matched for insulin sensitivity and did not differ in body mass index. Proinsulin and insulin secretion were measured after arginine stimulation (5 g, i.v.) at three glucose levels (fasting, 14 mmol/L, and >25 mmol/L), and the acute insulin (AIR(arg)) and proinsulin responses (APIR(arg)) were calculated as the mean 2-5 min postload increase. At fasting glucose, levels of insulin, proinsulin, or the proinsulin/insulin ratio (13.6 +/- 5.0% vs. 11.1 +/- 2.7%; P = NS) did not differ between NGT and IGT. Although the AIR(arg) values were decreased in the IGT group at all glucose levels (P < 0.05), the absolute proinsulin levels and the APIRs(arg) were similar between IGT and NGT women. Therefore, the IGT women had higher proinsulin/insulin ratios at 14 mmol/L (10.7 +/- 4.4% vs. 6.4 +/- 1.8%; P = 0.006) and more than 25 mmol/L glucose (11.4 +/- 5.2% vs. 6.7 +/- 2.1%; P = 0.007). The IGT group had increased APIR(arg)/AIR(arg) at fasting (2.2 +/- 1.4% vs. 1.3 +/- 0.6%; P = 0.047) and more than 25 mmol/L glucose (3.5 +/- 1.6% vs. 2.3 +/- 0.7%; P = 0.037). We conclude that women with IGT exhibit increased relative proinsulin secretion, suggesting a defect in the intracellular proinsulin processing before diabetes develops.
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PMID:Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance. 1037 12

In a longitudinal study of the effects of moderate (70%) dietary restriction (DR) on aging, plasma glucose and insulin concentrations were measured from semiannual, frequently sampled intravenous glucose tolerance tests (FSIGTT) in 30 adult male rhesus monkeys. FSIGTT data were analyzed with Bergman's minimal model, and analysis of covariance revealed that restricted (R) monkeys exhibited increased insulin sensitivity (S(I), P < 0.001) and plasma glucose disappearance rate (K(G), P = 0.015), and reduced fasting plasma insulin (I(b), P < 0.001) and insulin response to glucose (AIR(G), P = 0.023) compared with control (C; ad libitum-fed) monkeys. DR reduced the baseline fasting hyperinsulinemia of two R monkeys, whereas four C monkeys have maintained from baseline, or subsequently developed, fasting hyperinsulinemia; one has progressed to diabetes. Compared with only the normoinsulinemic C monkeys, R monkeys exhibited similarly improved FSIGTT and minimal-model parameters. Thus chronic DR not only has protected against the development of insulin resistance in aging rhesus monkeys, but has also improved glucoregulatory parameters compared with those of otherwise normoinsulinemic monkeys.
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PMID:Dietary restriction and glucose regulation in aging rhesus monkeys: a follow-up report at 8.5 yr. 1155 52


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