Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.
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PMID:Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes. 130 65

To examine the release of insulin in response to oral glucose, intravenous glucagon and intravenous arginine, we measured the levels of plasma glucose, immuno-reactive insulin (IRI) and C-peptide levels on fasting and following an oral glucose loading (OGTT), intravenous glucagon (GON) and arginine (ARG) infusion test in nine newly diagnosed non-insulin dependent diabetics. Their ages ranged from 38 to 65. The fasting plasma glucose and hemoglobin A1c levels were 240 +/- 14 mg/dl (Mean +/- SEM) and 10.7 +/- 0.54%, respectively. Mean values of the peak C-peptide/fasting C-peptide ratio and peak IRI/fasting IRI ratio were significantly increased, as compared with the basal level (P < 0.05), but not significantly different from those of the OGTT, GON and ARG test. In conclusion, the effect of arginine-induced insulin secretion in non-insulin dependent diabetes mellitus is as good as those of glucose or glucagon.
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PMID:Arginine induced insulin release in patients with newly onset non-insulin-dependent diabetes mellitus. 133 Feb 42

Glucokinase is thought to play a glucose-sensor role in the pancreas, and abnormalities in its structure, function, and regulation can induce diabetes. We isolated the human glucokinase gene, and determined its genomic structure including exon-intron boundaries. Structure of the glucokinase gene in human was very similar to that in rat. Then, by screening Japanese diabetic patients using polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) and direct-sequencing strategies, we identified a missense mutation substituting arginine (AGG) for glycine (GGG) at position 261 in exon 7 of the glucokinase gene in a patient with early-onset non-insulin-dependent diabetes (NIDDM).
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PMID:Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus. 146 39

The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2). In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo. Thus, nicardipine did not produce any significant overall alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects.
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PMID:Nicardipine does not cause deterioration of glucose homoeostasis in man: a placebo controlled study in elderly hypertensives with and without diabetes mellitus. 150 7

We used MK-912, a potent new selective alpha 2-adrenergic receptor antagonist that is active orally, to study the effect of short-term, selective alpha 2-blockade on fasting plasma glucose (FPG) and pancreatic islet function in non-insulin-dependent diabetes (NIDDM). Ten asymptomatic patients with NIDDM received either a single oral dose of MK-912 (2 mg) or placebo in a double-blind, cross-over study. B-cell function was measured by the acute insulin response (AIR) to glucose (1.66 mmol/kg intravenously [IV]) and by the AIR to arginine (5 g IV) during a hyperglycemic glucose clamp at a mean glucose level of 32.1 mmol/L to provide an estimation of maximal B-cell secretory capacity. A-cell function was estimated by the acute glucagon response (AGR) to arginine during the glucose clamp. Effective alpha 2-adrenergic blockade was apparently achieved, as there were substantial increases of plasma norepinephrine (NE) (P less than .01) and both systolic blood pressure (SBP) (P less than .01) and diastolic blood pressure (DBP) (P less than .05) after treatment with MK-912, but not after placebo. MK-912 caused a significant (P less than .05) although modest decrease of FPG that was associated with a small increase of fasting plasma insulin (P less than 0.01), C-peptide (P less than .05), and glucagon (P less than .01). FPG and hormone levels remained unchanged after placebo. MK-912 tended to increase the AIR (P = .06) and the C-peptide response (P = .07) to glucose compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of an oral alpha 2-adrenergic blocker (MK-912) on pancreatic islet function in non-insulin-dependent diabetes mellitus. 168 87

We investigated the dose-response characteristics of glucose-induced insulin release and the influence of hyperglycaemia on arginine-induced insulin secretion in eight non-obese subjects with NIDDM and in eight non-diabetic volunteers. Plasma C-peptide levels, achieved during 60 min hyperglycaemic clamps with and without the infusion of a primed continuous infusion of arginine (infusion rate 15 mg kg-1 min-1) during the last 30 min, were analysed with a modified Michaelis-Menten equation. The insulin secretory capacity (Vmax) for glucose-stimulated insulin release showed a trend towards a negative correlation with the fasting blood glucose in the NIDDM subjects (r = 0.68, P = 0.6); it was lower than the Vmax of non-diabetic controls (2.2 +/- 0.2 vs 4.2 +/- 0.4 nmol l-1 respectively; P less than 0.001). The ED50 (half maximal stimulating blood glucose concentration) of the second-phase glucose-stimulated insulin release (determined from the plasma C-peptide levels at 60 min) was not significantly different from the ED50 of the controls (11.9 +/- 0.8 vs 13.3 +/- 1.9 mmol l-1 respectively; P greater than 0.2). Combined glucose-arginine stimulation significantly increased insulin release. The Vmax for both phases were significantly lower in NIDDM patients than in controls (2.3 +/- 0.2 vs 5.0 +/- 0.9 and 3.8 +/- 0.5 vs 8.5 +/- 0.9 nmol l-1 respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased insulin secretory capacity and normal pancreatic B-cell glucose sensitivity in non-obese patients with NIDDM. 190 29

We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration. In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed that arginine stimulated the secretion of pancreatic glucagon (PG 33-61), major proglucagon fragment (PG 72-158) and probably GLP-1 (PG 72-107 amide) in both groups, whereas oral glucose stimulated the secretion of glicentin (PG 1-69) and intestinal GLP-1 (PG 78-107 amide), an insulinotropic hormone. The elevated levels of immunoreactive GLP-1 in diabetics in the fasting state were mainly due to an increased concentration of major proglucagon fragment.
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PMID:Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. 199 27

To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2 +/- 0.4; 20 nmol/h, 3.3 +/- 0.3; 30 nmol/h, 3.1 +/- 0.2 ml/kg.min; p less than 0.05 to p less than 0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3 +/- 0.4; obese, 1.0 +/- 0.2) than in healthy (2.0 +/- 0.3), or obese subjects with impaired glucose tolerance (2.8 +/- 0.7). Stimulated C-peptide/insulin ratio was reduced in all patients vs that in healthy subjects (p less than 0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.
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PMID:Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM. 207 83

The effect of islet surface antibodies (ICSA) on in vitro insulin release was studied. Isolated rat islets were incubated in the presence of immunoglobulin preparations from patients with insulin-dependent and non-insulin-dependent diabetes mellitus (IDDM, NIDDM) and healthy subjects, and stimulated with D-glucose, L-arginine or tolbutamide. After incubation, the amount of insulin release from the rat islets was determined. The immunoglobulin preparations from 5 newly diagnosed IDDM patients who were positive for ICSA, and from 5 age-matched healthy subjects were examined. Even in the absence of complement or lymphocytes, immunoglobulin fractions positive for ICSA significantly inhibited low and high concentrations of glucose-stimulated insulin release compared with normal control (P less than 0.02), but had little influence on insulin release after stimulation with tolbutamide. Arginine-stimulated insulin release was almost the same in ICSA-positive immunoglobulin fractions and the control. Immunoglobulin fractions negative for ICSA either from four patients with recently diagnosed IDDM or from four newly diagnosed NIDDM patients had only negligible effect on insulin release after stimulation with glucose. These results suggest that ICSA in IDDM patients, even in the absence of complement or lymphocytes, may preferentially interfere with the mechanisms of glucose-stimulated insulin release in the pancreatic B cells.
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PMID:Islet cell surface antibodies preferentially inhibit glucose-stimulated insulin release in vitro. 219 Jul 82

We have proposed that chronic hyperglycemia causes the abnormal glucose influence on arginine-stimulated insulin secretion in the neonatal streptozocin (STZ) rat model of NIDDM and therefore studied the effect of 24 h of mild insulin-induced hypoglycemia on this defect. Ultralente insulin, 20 U/kg, was given at 9 a.m. and 10 U/kg at 5 p.m., and insulin and glucagon secretion were then studied the next morning using the in vitro isolated, perfused pancreas. The fed plasma glucose concentrations decreased in the STZ rats from 191 +/- 13 to 101 +/- 9 mg/dl and from 133 +/- 4 to 99 +/- 8 mg/dl in the controls. As expected, 10 mM arginine caused a trivial insulin response at 2.8 mM glucose in the treated and untreated control groups compared with the marked one at 16.7 mM. The response to arginine at 2.8 mM glucose in the untreated STZ rats, however, was strikingly elevated (7.65 +/- 2.29 versus 0.41 +/- 0.16 ng/ml in the untreated controls) and it was not potentiated by the high glucose background, but the result at 2.8 mM glucose in the treated STZ rats was similar to that of the treated controls (0.46 +/- 0.12 versus 0.16 +/- 0.03 ng/ml). A return of glucose influence on IBMX-stimulated insulin secretion was also noted. Glucose-induced insulin release, however, was not restored in the treated STZ rats, but it was markedly suppressed in the controls by the insulin treatment. Glucose influence on the glucagon response to arginine was maintained in the STZ model even though the glucagon release to a lowered glucose concentration was lost.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Abnormal insulin secretion in a streptozocin model of diabetes. Effects of insulin treatment. 240 48


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