Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 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)
 ...
PMID:Increased beta-cell secretory capacity as mechanism for islet adaptation to nicotinic acid-induced insulin resistance. 265 28

The present investigation was designed to evaluate the effect of acute and protracted verapamil administration on insulin and glucagon secretion in man. For this purpose, 14 normal subjects received two consecutive glucose pulses (5 g.i.v. in less than 20 sec or 20 g.i.v. in less than 1 min, 7 subjects for each group), 70 or 90 min apart, before and during an infusion of verapamil (160 microgram/min). Seven additional normal subjects received two consecutive arginine pulses (5 g i.v.), 70 min apart. In 14 inpatients with coronary heart disease, we investigated the effect of protracted verapamil administration. Seven of these subjects underwent two oral glucose tolerance tests (100 g) and the other 7 two arginine tests (30 g) before and after a 10-day treatment with verapamil, 240 mg/die p.o. divided into three doses; the last dose, 80 mg, was given orally 1 h before the performance of the post-treatment test. Verapamil significantly inhibited the acute insulin response (AIR, mean change from 3-10 min) to glucose (5 g), as well as the AIR and AGR (acute glucagon response) to arginine (5 g). By contrast, verapamil failed to alter significantly the AIR to the higher glucose pulse. There was no significant change of oral glucose tolerance after verapamil, nor was there a change in insulin response to oral glucose. By contrast, insulin and glucagon responses to arginine infusion were significantly reduced by the drug.
 ...
PMID:Modulation by verapamil of insulin and glucagon secretion in man. 701 49

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.
 ...
PMID:Glucose modulation of insulin and glucagon secretion is altered in impaired glucose tolerance. 777 22

Insulin sensitivity and islet function were examined in 22 obese women: 11 with normal glucose tolerance (mean +/- SD body mass index [BMI], 32.2 +/- 2.8 kg/m2) and 11 with impaired glucose tolerance (BMI, 30.1 +/- 2.2 kg/m2). Thirteen non-obese women with normal glucose tolerance (BMI, 20.9 +/- 1.3 kg/m2) served as controls. All women were 58 to 59 years of age. Insulin sensitivity was measured with the euglycemic, hyperinsulinemic clamp. Insulin secretion was studied after intravenous arginine (5 g) at fasting, and at blood glucose levels of 14 and greater than 25 mmol/L. Insulin sensitivity was higher in non-obese (99.8 +/- 11.5 nmol/kg/min/pmol insulin/L) than in obese subject (P < or = .002), but did not differ between obese subjects with normal versus impaired glucose tolerance (47.2 +/- 8.8 v 45.5 +/- 5.2 nmol/kg/min/pmol insulin/L, difference not significant [NS]). Obese subjects with normal glucose tolerance had a higher insulin response to both glucose (P < or = .004) and arginine (P < or = .02) than nonobese women, and higher glucose potentiation of insulin secretion, slopeAIR (P = .05). Compared with obese subjects with normal glucose tolerance, the obese subjects with impaired glucose tolerance had a lower insulin response to glucose (P = .03) and to arginine at blood glucose levels of 14 mmol/L (P = .03), as well as a lower slopeAIR levels ( P = .03). Fasting glucagon was higher in obese subjects with normal glucose tolerance than in non-obese subjects with normal glucose tolerance (P = .006). In obese subjects with impaired glucose tolerance, the glucose inhibition of glucagon secretion, slope AGR, was lower than in obese subjects with normal glucose tolerance (P = .04). Thus, obese subjects with impaired glucose tolerance have altered glucose modulation of islet function, mainly manifested as reduced slope AIR and slope AGR, yet insulin sensitivity is not different than in equally obese subjects with normal glucose tolerance. We therefore conclude that islet dysfunction, and not a further reduction of insulin sensitivity, determines the development of impaired glucose tolerance in obesity.
 ...
PMID:Islet dysfunction in obese women with impaired glucose tolerance. 860 39

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.
 ...
PMID:Impact of family history of diabetes on the assessment of beta-cell function. 959 41

Quantitative determination of insulin secretion is of importance both clinically and in research. The optimal method has not been established, although several different methods have been used. We determined the reproducibility of islet function parameters obtained by the glucose-dependent arginine stimulation test, and also studied the priming effect of arginine on subsequent acute insulin responses. The test measures the acute insulin (AIR) and glucagon (AGR) responses to i.v. arginine (5 g injected over 45 s) at fasting glucose and glucose concentrations clamped at 14 and above 25 mmol/l, as well as the glucose potentiation of insulin secretion (slopeAIR) and the glucose inhibition of glucagon secretion (slopeAGR). When the test was performed twice in seven healthy women (mean +/- SD age 58.7 +/- 0.5 years, BMI 27.6 +/- 5.5 kg/m2), the AIRs to arginine had a within-subject coefficient of variation (CV) of 18.6% at fasting glucose, 18.7% at 14 mmol/l glucose and 16.3% at above 25 mmol/l glucose. The CVs for AGR were 11.6, 14.9 and 8.9%, respectively. The CV of the slopeAIR was 24% and of the slopeAGR 17.2%. The arginine priming study was performed in six healthy women (age 63.7 +/- 0.3 years, BMI 28.0 +/- 6.9 kg/m2). Saline or arginine (5 g) was injected at fasting glucose, followed by arginine (5 g) at 14 mmol/l glucose. There was no difference between the acute insulin or glucagon responses to arginine at 14 mmol/l glucose in the two conditions, suggesting that there is no priming effect of arginine on the subsequent acute insulin or glucagon responses. Therefore, this method is a good tool to determine insulin secretion as, apart from its good reproducibility, it also provides several important parameters of islet function.
 ...
PMID:Glucose-dependent arginine stimulation test for characterization of islet function: studies on reproducibility and priming effect of arginine. 968 17

Beta-cell function in growth hormone (GH)-deficient (GHD) adults is poorly documented. Beta-cell function was therefore studied in 10 GHD adults (age, 40+/-3 years; weight, 79.3+/-4.8 kg; body mass index [BMI], 27.5+/-1.3 kg x m(-2)) before and after 6- and 24-month recombinant human GH (rhGH) therapy (0.24 IU x kg(-1) x wk(-1)) compared with 10 age-, sex-, weight-, and BMI-matched control subjects. With rhGH therapy, fat-free mass (FFM) increased (48.2+/-4.9, 52.5+/-4.8, and 59+/-6.8 kg, respectively) and fat mass (FM) decreased (33.8%+/-2.8%, 28.0%+/-3.0%, and 29.4%+/-2.5%, respectively), as did serum cholesterol. Oral glucose tolerance initially deteriorated at 6 months, but improved toward the control value by 24 months. Fasting insulin (FI) increased significantly, as did the acute insulin response to oral glucose (deltaAIR(OGTT)/deltaG) at 30 minutes (FI: pretreatment 9.8+/-0.8, 6 months, 14.0+/-1.8, 24 months 12.5+/-1.6 v control 11.4+/-1.9 mU x L(-1); deltaAIR(OGTT)/deltaG: pretreatment 201+/-24, 6 months 356+/-41, 24 months 382+/-86 v control 280+/-47 mU x mmol(-1)). However, the acute insulin response to intravenous (IV) glucose (AIR(G)) and IV glucagon at euglycemia and hyperglycemia did not change with rhGH therapy and were similar to the control group values. Importantly, the expected reciprocal relationships (as observed for the control group) between the various insulin secretory parameters and insulin sensitivity (SI) either were not present or were statistically weak in GHD subjects, despite the 35% decrease in SI by 24 months of rhGH therapy. In particular, over time, there was an attenuation of insulin secretion with respect to the ongoing insulin resistance with rhGH therapy, particularly for AIR(G) at 24 months. After 5 days of rhGH withdrawal, insulin secretion decreased and SI improved in GHD subjects. It is concluded that the current long-term rhGH treatment regimens appear to impact on insulin secretion such that the normal relationships between insulin secretion and SI are altered despite the favorable impact on body composition and serum lipid profiles.
 ...
PMID:Insulin secretion in growth hormone-deficient adults: effects of 24 months' therapy and five days' acute withdrawal of recombinant human growth hormone. 1058 46

To study whether antibodies to glutamic acid decarboxylase (GADab) are associated with subclinical beta-cell damage and impaired insulin secretion, we screened 441 nondiabetic patients with autoimmune thyroiditis (AT) for GADab, and 15 (3.4%) were found positive. Antibodies to IA-2 were found in two GADab+ and one GADab- patients. We matched 11 GADab+ and 13 GADab- AT patients who were euthyroid on thyroxin supplementation, and 13 control subjects for sex, age, and body mass index and measured insulin, C-peptide, and glucagon response to glucose and arginine at three blood glucose concentrations (fasting, 14 mmol/liter, >25 mmol/liter). In the fasting state, all groups had similar blood glucose concentration and HbA1c level, but the serum insulin concentration was higher in the AT patients compared with the control subjects (P < 0.04). The acute insulin response to arginine was lower in GADab+ than in GADab- thyroiditis subjects at glucose concentration of 14 and >25 mmol/liter (AIR(14): 76.8 +/- 52.0 vs. 158.2 +/- 118.2 mU/liter, P = 0.040; AIR(>25): 84.3 +/- 64.4 vs. 167.9 +/- 101.5 mU/liter, P = 0.035). In conclusion, GADab were associated with a decreased insulin secretion capacity in nondiabetic subjects with thyroiditis, which suggests that GADab positivity could be a marker of subclinical insulitis.
 ...
PMID:Glutamic acid decarboxylase antibody positivity is associated with an impaired insulin response to glucose and arginine in nondiabetic patients with autoimmune thyroiditis. 1188 83

Islet function was examined in 13 severely obese women [body mass index 46.4 +/- 5.5 (SD) kg/m(2)] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR(1)), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37-50% after 15 and 25% WR (P <or= 0.05). Insulin sensitivity was determined as the amount of glucose infused to reach 14 mmol/l divided by the insulin level (M/I), a measure showing a linear correlation with insulin sensitivity during euglycemic hyperinsulinemic clamps (r = 0.74, P < 0.001) and a hyperbolic relation to AIR(1) (r = -0.63, P < 0.001) in 169 healthy subjects. M/I was increased by 318 +/- 182% after 15% (P = 0.004) and by 489 +/- 276% after 25% WR (P = 0.007). The reduction in insulin secretion was not as large as anticipated from the increased insulin sensitivity, which resulted in an increased disposition index (DI; AIR(1) x M/I). Thus DI increased by 95 +/- 24% after 15% (P = 0.018) and by 176 +/- 35% after 25% WR (P = 0.011). This improved beta-cell function correlated independently with reduced glucose, triglycerides, and leptin and increased adiponectin levels and was associated with a reduced proinsulin-to-insulin ratio. In contrast, glucagon secretion was not significantly affected by WR. We conclude that WR results in improved beta-cell function when related to insulin sensitivity.
 ...
PMID:Improved beta-cell function after standardized weight reduction in severely obese subjects. 1255 52

Various stimuli have been used in clinical practice to test islet function, including intravenous glucose, arginine--both at basal glucose levels and with the hyperglycaemic clamp, tolbutamide, glucagon and glucagon-like peptide 1. The subsequent first phase insulin response (also termed acute insulin response or AIR) to intravenous glucose or arginine has been quantified in a variety of ways, from the mean serum insulin measured at multiple times after glucose injection to the mean value above baseline of serum insulin at 2 to 10 min. The purpose of this study was to review the different protocols of AIR calculation and their pitfalls, and to assess the results of AIR in the islet transplantation field. By investigating the first phase of insulin secretion, AIR provides both a qualitative and a quantitative approach to insulin secretion. In islet transplantation, post-glucose AIR (AIRg) may predict graft survival while post-arginine AIR (AIRa) may be better correlated with engrafted beta cell mass, despite these facts need to be confirmed. AIRa also limits intravenous hyperglycaemia glucotoxicity. In conclusion, AIR could help to predict the need for a second or third islet injection in islet transplantation. These specific indications, however, need to be confirmed by future studies and completed by other approaches such as insulin sensitivity studies and in vivo morphological assessment of islet mass.
 ...
PMID:Acute insulin response (AIR): review of protocols and clinical interest in islet transplantation. 1697 56


1 2 Next >>