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)

Islet amyloid polypeptide (IAPP) is a 37-amino acid residue polypeptide, originally isolated from the pancreatic amyloid deposits of patients with type II diabetes mellitus. Subsequently, IAPP was found to be colocalised with insulin in beta-cell secretory granules of the normal mammalian pancreas. Recently, IAPP has been reported to inhibit glucose-stimulated insulin release from isolated rat islets and to be released in response to glucose and arginine. To investigate further the regulation of IAPP release from the islet, we used a previously developed specific radioimmunoassay for IAPP and measured IAPP secretion from isolated rat islets of Langerhans. Release of IAPP-like immunoreactivity (-LI) was stimulated by glucose: 3.3 +/- 0.3, 3.9 +/- 0.3, and 11.1 +/- 1.5 (n = 5, mean +/- SEM) fmol/islet/60 min at 2, 7, and 20 mM, respectively. Carbachol (0.1 mM) increased the release of IAPP-LI at the lower glucose concentrations: 8.1 +/- 0.9, 8.7 +/- 0.6, and 11.7 +/- 1.8 fmol/islet/60 m in at 2, 7, and 20 mM glucose. Somatostatin (1 microM) suppressed glucose-stimulated IAPP-LI release (17.5 +/- 1.5 vs. 5.1 +/- 0.5 fmol/islet/60 min). Chromatographic characterisation of the IAPP-LI released into the incubation medium revealed two immunoreactive forms: The major peak (74% of the total IAPP-LI) corresponded to synthetic IAPP-37, while a smaller form, comprising 26% IAPP-LI, eluted later. In acid extracts of islets, all (> 95%) immunoreactivity co-eluted with the synthetic IAPP.
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PMID:Molecular form of islet amyloid polypeptide (amylin) released from isolated rat islets of Langerhans. 846 Jan

Endothelin-1 (ET-1) causes dramatic vasoconstriction and reduction of renal blood flow, with a decreased glomerular filtration rate (GFR). Early diabetic nephropathy is characterized by elevation of GFR and the formation of intrarenal microaneurysms. However, the mechanisms are unclear. To elucidate the pathophysiologic significance of urinary ET-1 in early diabetic nephropathy, the 24-h urinary excretion of ET-1 in 12 normal subjects and 20 patients with newly diagnosed type 2 diabetes mellitus were determined by a highly sensitive radioimmunoassay. The 24-h urinary ET-1 excretion in patients with diabetes mellitus (14.2 +/- 3.1 pmol, mean +/- SEM) was significantly lower (p < 0.05) than that of normal subjects (25.0 +/- 3.7 pmol). This decrease in urinary excretion of ET-1 in patients with recent-onset diabetes mellitus suggests a possible role of ET-1 in the pathogenesis of early diabetic nephropathy.
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PMID:Does endothelin play a role in the pathogenesis of early diabetic nephropathy? 858 52

The 75-g oral glucose tolerance test was performed in 38 normoglycaemic (World Health Organization criteria) non-diabetic volunteers, aged 31-40 years, of whom 20 had a non-insulin-dependent diabetic (NIDDM) mother and 18 had an NIDDM father. At the time of the study the offspring of NIDDM mothers had a somewhat higher body mass index (BMI) (males: 26.5 +/- 1.0 (mean +/- SEM), females: 27.5 +/- 1.5 kg/m2) than the offspring of NIDDM fathers (males: 23.4 +/- 0.9, females: 24.2 +/- 1.2 kg/m2). There was no difference in the time-course of glycaemia; however the serum concentrations of immunoreactive insulin (IRI), C-peptide and proinsulin were significantly higher in offspring of NIDDM mothers than in offspring of NIDDM fathers: area under the curve (AUC) serum IRI: 0.928 +/- 0.091 vs 0.757 +/- 0.056 nmol.l-1.h-1, p = 0.019; serum C-peptide: 6.379 +/- 0.450 vs 4.753 +/- 0.242 nmol.l-1.h-1, p = 0.004; serum proinsulin: 172 +/- 40 vs 51 +/- 7 pmol.l-1.h-1, p = 0.008). Serum IRI correlated with BMI, but C-peptide and proinsulin did not, and after accounting for BMI by covariance analysis they remained significantly higher in offspring of NIDDM mothers. In this group serum proinsulin was significantly higher in male than in female offspring (AUC serum proinsulin: 289 +/- 68 vs 77 +/- 27 pmol.l-1.h-1, P = 0.015). Male offspring of NIDDM mothers also had significantly higher serum triglyceride levels than females of the same group and than offspring of NIDDM fathers. The offspring (male and female) of NIDDM mothers had slightly lower serum apolipoprotein A-I levels than the offspring of NIDDM fathers. Significant correlations were found between serum triglycerides, HDL-cholesterol and apolipoprotein B, and serum concentrations of pancreatic beta-cell peptides, mostly in the offspring of NIDDM mothers; however, they did not display unequivocal association with gender within this group. The data are consistent with clinical observations of a greater risk of NIDDM transmission from the mother than from the father, and may suggest that male offspring are more exposed to this risk than female offspring.
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PMID:Difference in the influence of maternal and paternal NIDDM on pancreatic beta-cell activity and blood lipids in normoglycaemic non-diabetic adult offspring. 881 8

To measure possible changes in basal and insulin-stimulated phosphotyrosine phosphatase (PTPase) activity in skeletal muscle from insulin-resistant individuals, soluble and particulate muscle fractions were prepared from biopsies taken before and after a 3-h hyperinsulinaemic euglycaemic clamp in eight non-insulin-dependent diabetic (NIDDM) patients and nine control subjects. We used a sensitive sandwich-immunofluorescence assay and the human insulin receptor as the substrate. PTPase activity was expressed as percentage of dephosphorylation of phosphotyrosyl-residues in immobilized insulin receptors per 2 h incubation time per 83 micrograms and 19 micrograms muscle fraction protein (soluble and particulate fraction, respectively). In the diabetic soluble muscle fractions, the basal PTPase activity was decreased compared with that of control subjects (11.5 +/- 5.5 vs 27.5 +/- 3.3, p < 0.04, mean +/- SEM). In the particulate muscle fractions from the control subjects, PTPase activity was increased after 3 h hyperinsulinaemia (20.0 +/- 3.2 vs 30.2 +/- 3.6, p < 0.03) and in the corresponding soluble fractions PTPase activity seemed decreased (27.5 +/- 3.3 vs 19.9 +/- 5.9, NS). No effect of insulin on PTPase activity was found in NIDDM patients (25.1 +/- 4.1 vs 27.2 +/- 5.2, 11.5 +/- 5.5 vs 15.1 +/- 4.5 [particulate and soluble fractions], NS). In conclusion, we found that the basal PTPase activity in soluble muscle fractions was decreased in NIDDM patients; furthermore, insulin stimulation was unable to increase PTPase activities in the particulate fractions, as opposed to the effect of insulin in control subjects.
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PMID:Altered basal and insulin-stimulated phosphotyrosine phosphatase (PTPase) activity in skeletal muscle from NIDDM patients compared with control subjects. 889 9

We have recently demonstrated the nocturnal increase in leptin secretion in humans. In the present study we have examined the pulsatile pattern of leptin secretion using two different experimental protocols. The first protocol utilized blood samples withdrawn at 30 minute intervals immediately after meals, at 1 hour intervals between meals, and at 2 hour intervals during the night from 4 lean, 11 obese, and 5 obese NIDDM subjects. Analysis of circulating leptin levels by ULTRA algorithmic program and using matched intra-assay coefficient of variations demonstrated 1 to 7 ultradian oscillations with a mean of 3.25 +/- 0.36 (SEM) pulses per 24 hour period (period: 10.0 +/- 1.5 hours; mean relative amplitude: 0.52 +/- 0.06, n = 20). Significant positive correlations were observed for changes in absolute amplitude with body mass index (p < 0.025) and fasting leptin levels (< 0.0001). In the second series of experiments utilizing 15 minute blood sampling from 10 overnight fasted obese subjects (BMI 35.9 +/- 2.0 kg/m2), ultradian oscillations for leptin were more frequent, i.e., 2 to 7 oscillations (4.20 +/- 0.59), over a 12 hour duration (period: 3.44 +/- 0.49; mean relative amplitude: 0.28 +/- 0.03). The number of oscillations over a 12 hour period correlated significantly with BMI (p < 0.001), fasting leptin levels (p < 0.01), and absolute amplitude (p < 0.005) in a 15 minute sampling protocol. In summary, similar to other hormones, ultradian oscillations of leptin are observed in humans, although the physiological significance in relation to obesity or feeding behavior is not yet understood.
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PMID:Ultradian oscillations of leptin secretion in humans. 894 46

Sixteen patients with type 2 diabetes poorly controlled by glibenclamide (7.5-10.0 mg/day) were treated with acarbose (100 mg tds) for one week and the effect on the blood glucose profile, 24-hour urinary glucose excretion, plasma fructosamine, and plasma 1,5-anhydro-D-glucitol (1,5-AG) level was determined. The blood glucose profile was more stable and levels were lower during acarbose administration. In some patients, this improvement was maintained after discontinuing acarbose. The M-value, an indicator of blood glucose fluctuations, decreased significantly from 33.2 +/- 3.0 (mean +/- SEM) in the run-in period to 13.4 +/- 2.4 during acarbose therapy (P < 0.001), and rose again to 26.5 +/- 4.4 (P < 0.001) in the follow-up period. The 24-hour urinary glucose excretion and plasma fructosamine decreased similarly (P < 0.001 and P < 0.01, respectively) during and after acarbose therapy. Plasma 1,5-AG levels did not change significantly during acarbose therapy, but increased markedly afterwards (from 19.3 +/- 3.1 mumol 1(-1) to 25.0) +/- 3.1 mumol l-1, P < 0.001). Plasma 1,5-AG levels were significantly correlated with urinary glucose excretion one week earlier (r = 0.513, P < 0.006). These findings suggest that acarbose may improve glycemic control in type 2 diabetic patients poorly controlled by sulfonylurea therapy and that plasma 1,5-AG might be used as a marker of glycemic control cooperating with other markers such as fructosamine and urinary glucose determination for monitoring the short-term response to antidiabetic therapy.
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PMID:Effect of acarbose on blood glucose profiles and plasma 1,5-anhydro-d-glucitol in type 2 diabetes poorly controlled by sulfonylurea therapy. 895 71

Urinary iron excretion rate(u-FeER, microgram/min) in urine at night time from 58 patients with non-insulin dependent diabetes mellitus and 8 controls was measured by atomic absorption. The patients were divided into three groups according to urinary albumin excretion rate(u-AER), namely, Group I(n = 44): less than 20 micrograms/min of u-AER; Group II(n = 9): 20 < or = u-AER < 200 micrograms/min; Group III(n = 5): more than 200 micrograms/min of u-AER. The u-FeER in group III(56.3 +/- 14.8 ng/min, mean +/- SEM) was significantly higher than that in controls (4.0 +/- 1.6ng/min), group I(8.3 +/- 1.6 ng/min) and group II(18.5 +/- 6.5ng/min). The increase of u-FeER in group III indicates that urinary iron may at least partly play a role in development of diabetic nephropathy.
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PMID:[Increased urinary iron excretion rate in patients with non-insulin dependent diabetes mellitus]. 899 Sep 41

The C-peptide suppression test employing the euglycemic hyperinsulinemic clamp technique has been proposed as a useful diagnostic measure for insulinoma. To examine the specificity of the C-peptide suppression, we applied this test to subjects with symptoms suggesting reactive hypoglycemia. Five subjects studied had never experienced fasting hypoglycemia, and were negative in ultrasound, CT and MRI of the pancreas. Plasma C-peptide was not suppressed by physiological (50-100 microU/ml) and supraphysiological (200-500 microU/ml) hyperinsulinemia (% of baseline: 97.3 +/- 8.6% and 90.6 +/- 10.4%, +/- SEM, respectively, both NS). Three subjects were re-examined one year later, when their hypoglycemic episodes were noticeably attenuated. No significant suppression was found. Significant suppression was observed when plasma glucose was clamped at 50-60 mg/dl in four of five subjects (61.7 +/- 11.5%, P < 0.05), but one subject responded to neither higher plasma insulin nor low-normal glucose. In contrast, normal glucose tolerance (n = 13), IGT (n = 12) and obese NIDDM (n = 31) subjects showed highly significant suppression during euglycemic and physiological hyperinsulinemia (37.1 +/- 3.8%, 46.3 +/- 5.6%, 39.9 +/- 2.6%, respectively, all P < 0.001). In conclusion, the results of the present study indicate that a failure of hyperinsulinemic suppression of C-peptide in euglycemia is not specific for insulinoma, and that suppression of C-peptide by insulin at lower plasma glucose levels (50-60 mg/dl) would be a better diagnostic test.
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PMID:Lack of C-peptide suppression by exogenous hyperinsulinemia in subjects with symptoms suggesting reactive hypoglycemia. 907 3

The influence of exercise on glycaemia in the post-prandial state was studied for the first time in non-insulin-dependent diabetic (NIDDM) patients. Meal-induced glucose responses were followed for 8 h in 9 diet-treated patients with NIDDM. Subjects consumed a standardized breakfast and 4 h later a standardized lunch. They were studied in the resting state (control day (CD)) and on another day 45 min of bicycle exercise (53 +/- 2% VO2max (mean +/- SEM)) was performed 45 min after breakfast (exercise day (ED)). On day 3 (diet day (DD)), the breakfast meal was reduced corresponding to the extra energy expenditure during the exercise period on ED. Responses were calculated as areas under the plasma concentration curve (AUC) during 4 h after either breakfast (B-AUC) or lunch (L-AUC). B-AUC for glucose was identical on ED (215 +/- 63 mmol/l.240 min) and DD (219 +/- 60 mmol/l.240 min) and on these days lower (p < 0.05) than on CD (453 +/- 78 mmol/l.240 min). L-AUC for glucose on CD, ED and DD did not differ significantly. B-AUCs for both insulin and C-peptide were also significantly lower on ED and DD as compared to CD (Insulin: 31337 +/- 8682, 26092 +/- 6457 and 47649 +/- 15046 mmol/l.240 min, respectively. C-peptide: 99 +/- 19, 104 +/- 26 and 195 +/- 31 pmol/ml.240 min, respectively). Rate of appearance (Ra) for glucose was unaffected by exercise whereas rate of disappearance (Rd) increased significantly. No differences in Ra or Rd were observed after lunch. In conclusion, post-prandial exercise of moderate intensity decreases glycaemia and plasma insulin levels after breakfast in NIDDM patients, but this effect does not persist during and after the following lunch meal. Reduction of breakfast caloric intake has the same effect on post-prandial glycaemia and insulin secretion as an equivalent exercise-induced increase in caloric expenditure.
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PMID:The effect of moderate exercise on postprandial glucose homeostasis in NIDDM patients. 911 22

Increased triglyceride accumulation has been observed in the diabetic heart, but it is not known whether the abnormalities in myocardial fatty acid metabolism differ between insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients or whether they are present even prior to overt diabetes. Therefore, we studied myocardial fatty acid kinetics with single-photon emission tomography using 123I-heptadecanoic acid (HDA) in four groups of men: impaired glucose tolerance (IGT) (n = 13, age 53 +/- 2 years, mean +/- SEM), IDDM (n = 8, age 43 +/- 3 years), NIDDM (n = 10, age 51 +/- 2 years) and control subjects (n = 8, age 45 +/- 4 years). Echocardiography and myocardial perfusion scintigraphy (IGT and NIDDM groups) were performed to study cardiac function and flow. In the IGT subjects, myocardial HDA beta-oxidation index was reduced by 53% (4.6 +/- 0.4 vs 9.7 +/- 1.0 mumol .min-1.100 g-1, p < 0.01) and HDA uptake by 34% (3.7 +/- 0.2 vs 5.6 +/- 0.3% of injected dose 100g, p < 0.01) compared with the control subjects. The fractional HDA amount used for beta-oxidation was lower in the IGT compared with the control subjects (43 +/- 4 vs 61 +/- 4%, p < 0.05). NIDDM patients also tended to have a lowered HDA beta-oxidation index, whereas IDDM patients had similar myocardial HDA kinetics compared to the control subjects. Myocardial perfusion imaging during the dipyridamole-handgrip stress was normal both in the IGT and NIDDM groups, indicating that abnormal myocardial perfusion could not explain abnormal fatty acid kinetics. In conclusion, even before clinical diabetes, IGT subjects show abnormalities in myocardial fatty acid uptake and kinetics. These abnormalities may be related to disturbed plasma and cellular lipid metabolism.
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PMID:Abnormal myocardial kinetics of 123I-heptadecanoic acid in subjects with impaired glucose tolerance. 916 22


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