Failure to detect Glut4-Ile383 and IR-Gln1152 variants in NIDDM (non-insulin dependent diabetes mellitus) and control subjects in an Italian population

1995 ◽  
Vol 95 (1) ◽  
Author(s):  
Laura Esposito ◽  
Paola Carrera ◽  
AntonioEttore Pontiroli ◽  
Maurizio Ferrari
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Italian Population ◽  
Control Subjects ◽  
Insulin Dependent ◽  
And Control

Vascular responsiveness and cation exchange in insulin-dependent diabetes

1991 ◽  
Vol 81 (2) ◽  
pp. 223-232 ◽  
Author(s):  
Amir Halkin ◽  
Nigel Benjamin ◽  
Hilary S. Doktor ◽  
Sally D. Todd ◽  
Giancarlo Viberti ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Vascular Resistance ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Insulin Dependent ◽  
And Control ◽  
Forearm Vascular Resistance

1. We measured forearm blood flow during brachial artery infusions of vasoconstrictors (angiotensin II and noradrenaline) and vasodilators (sodium nitroprusside and carbachol) in 16 healthy control subjects and in 18 patients with uncomplicated insulin-dependent diabetes mellitus. Erythrocyte Na+/Li+ countertransport and platelet Na+/H+ antiport activities were also measured. 2. The mean basal forearm vascular resistance was 22% lower in diabetic patients than in control subjects. The effects of each infusion on forearm vascular resistance were similar in diabetic patients and control subjects. 3. Erythrocyte Na+/Li+ countertransport activities were similar in diabetic patients and control subjects. Platelet Na+/H+ exchange (Vmax.) was approximately 40% greater in diabetic patients than in control subjects, whereas the Km for Na+ was similar. 4. In diabetic patients, but not in control subjects, the responses to sodium nitroprusside and carbachol correlated inversely with Na+/Li+ countertransport in erythrocytes (rs = −0.76, P < 0.001, and rs = −0.66, P < 0.005, respectively), but not with Na+/H+ exchange in platelets.

Effect of Insulin-Dependent Diabetes Mellitus on Lipids and Lipoproteins: A Study of Identical Twins

1993 ◽  
Vol 84 (5) ◽  
pp. 537-542 ◽  
Author(s):  
Simon W. Dubrey ◽  
David A. Reaveley ◽  
David G. Leslie ◽  
Martina O'Donnell ◽  
Bernadette M. O'Connor ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Insulin Dependent Diabetes Mellitus ◽  
High Density ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Control Subjects ◽  
Insulin Dependent ◽  
Lipids And Lipoproteins

1. Forty-five identical twin pairs, discordant for insulin-dependent diabetes mellitus, were studied with respect to their serum lipid (high-density lipoprotein, low-density lipoprotein, total cholesterol and triacylglycerol) and apoprotein [apoprotein A-I, apoprotein B and lipoprotein (a)] concentrations and apoprotein (a) phenotypes. The twins were compared with an age- and sex-matched non-diabetic control group. 2. A significantly higher value was found only for high-density lipoprotein cholesterol in the diabetic twins of the female twin pairs. 3. Highly significant correlations existed between the twin pairs for all lipids and lipoproteins measured, particularly lipoprotein (a), for which identical apoprotein (a) isoforms were also found. 4. Correlations existed between the non-diabetic twins and the control subjects for high-density lipoprotein cholesterol and apoprotein A-I, probably due to the rigorous matching of control subjects. 5. The similarity between values for lipids and lipoproteins in the non-diabetic twins and control subjects suggested no effect of a genetic susceptibility to insulin-dependent diabetes mellitus. The differences in lipoproteins we describe for the identical twins discordant for insulin-dependent diabetes mellitus, in whom there was no evidence of a raised urinary albumin excretion rate, does not appear to explain the excess mortality from cardiovascular disease reported in patients with this disease.

Glyoxalase System in Clinical Diabetes Mellitus and Correlation with Diabetic Complications

1994 ◽  
Vol 87 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Antony C. McLellan ◽  
Paul J. Thornalley ◽  
Jonathan Benn ◽  
Peter H. Sonksen
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Haemoglobin A1c ◽  
Glyoxalase System ◽  
Control Subjects ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic

1. The metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus (n = 43), patients with non-insulin-dependent diabetes mellitus (n = 107) and 21 normal healthy control subjects. 2. The concentrations of glyoxalase metabolites, methylglyoxal, S-D-lactoylglutathione and D-lactate, were increased in diabetic patients, relative to normal control subjects: methylglyoxal [median, range (n) pmol/g], insulin-dependent patients, 470.7, 85.6-1044.3 (42), P < 0.001, non-insulin-dependent patients, 286.8, 54.7-2370 (105), P < 0.001, control subjects, 79.8, 25.3-892.9 (21); S-D-lactoylglutathione [mean ± SD (n) pmol/106 erythrocytes], combined diabetic patients, 3.37 ± 0.85 (24), control subjects 4.76 ± 1.95 (8) P < 0.05; D-lactate [mean ± SD or median, range (n) nmol/g], insulin dependent patients, median 18.3, 5.7-57.4 (42), P < 0.001, non-insulin-dependent patients, 20.0 ± 8.9, 2.6-48.4 (105), P < 0.001, control subjects 9.7 ± 4.3, 1.8-19.7 (21). The reduced glutathione concentrations in blood samples from the insulin-dependent and non-insulin-dependent diabetic patient groups were not different from the control group values (P>0.05). 3. The activities of glyoxalase enzymes in erythrocytes were increased: glyoxalase I activity [mean ± SD (n) m-units/106 erythrocytes] was increased in diabetic patients, relative to normal control subjects: insulin-dependent patients, 4.35 ± 1.54 (41), P < 0.001; non-insulin-dependent patients, 4.61 ± 1.79 (101), P < 0.001; control subjects, 3.21 ± 1.81 (21); glyoxalase II activity [mean ± SD (n) m-units/106 erythrocytes] was increased in the non-insulin-dependent diabetic patient group, relative to normal control subjects [non-insulin-dependent diabetic patients, 2.10 ± 0.46 (102); subject controls, 1.83 ± 0.27 (21); P < 0.05]. 4. In insulin-dependent diabetic patients, the concentration of methylglyoxal correlated positively with the duration of diabetes, and the concentration of D-lactate correlated positively with haemoglobin A1c and negatively with the reduced glutathione concentration. D-Lactate concentration correlated positively with blood glucose concentration in patients with non-insulin-dependent diabetes mellitus. 5. There was a positive logistic correlation of duration of disease with retinopathy, nephropathy, neuropathy, or any combination thereof. Retinopathy also gave a positive logistic correlation with haemoglobin A1c concentrations and a negative logistic correlation with D-lactate concentration. 6. When paired for duration of diabetes, patients with retinopathy, neuropathy or nephropathy, or any combination thereof, had significantly higher age, level of haemoglobin A1c and glyoxalase I activity than patients with uncomplicated diabetes (P < 0.05). 7. We conclude that the glyoxalase system is modified in erythrocytes in both insulin-dependent and non-insulin-dependent diabetic patients and that this modification is related to the development of diabetic complications.

Plasma Endothelin Levels and Vascular Effects of Intravenous l-Arginine Infusion in Subjects with Uncomplicated Insulin-Dependent Diabetes Mellitus

1994 ◽  
Vol 87 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Ronald A. Smulders ◽  
Coen D. A. Stehouwer ◽  
Cornelis G. Olthof ◽  
Gerard J. Van Kamp ◽  
Tom Teerlink ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Extracellular Fluid ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Diabetic Patients ◽  
Vascular Effects ◽  
Arginine Infusion ◽  
Control Subjects ◽  
Insulin Dependent

1. Uncomplicated insulin-dependent diabetes mellitus is associated with generalized vasodilatation. This vasodilatation is believed to contribute to the development of microvascular complications. The endothelium plays an important role in the regulation of vascular tone. 2. To investigate the role of endothelial mediators, we measured plasma endothelin levels and studied the vascular effects of intravenous l-arginine (the precursor of NO) in 10 male type 1 diabetic patients and 10 non-diabetic subjects. 3. The baseline plasma endothelin level was significantly lower in the diabetic patients [mean 1.7 (SD 0.5) versus 2.1 (0.4) pmol/l; P < 0.05] than in the control subjects. 4. During l-arginine infusion, plasma cyclic GMP (the second messenger for NO) increased in the control subjects [from 5.1 (2.9) to 6.9 (2.9) nmol/l; P < 0.05 versus saline] and in the diabetic patients [from 4.6 (1.8) to 5.7 (2.2) nmol/l; P = 0.09]. l-Citrulline (a by-product of NO synthesis from l-arginine) increased in both groups. The responses to l-arginine were not significantly different between the control subjects and the diabetic patients. The plasma atrial natriuretic peptide level did not change in either group during infusion of l-arginine or of an equal volume of isotonic saline. 5. Blood pressure decreased slightly during l-arginine administration in both groups. In control subjects, the extracellular fluid volume in the lower leg increased during l-arginine infusion as compared with saline; in the diabetic patients both l-arginine and saline increased the extracellular fluid volume. 6. In conclusion, the vascular effects of l-arginine are similar in men with uncomplicated insulin-dependent diabetes mellitus and in control subjects. Whether these effects are due to an increase in NO synthesis remains unclear. The increase in extracellular fluid volume during saline infusion in diabetic patients suggests an increase in microvascular permeability in

Enhanced Effects of Insulin and Angiotensin II on Intracellular pH and Free Cytosolic Calcium in Fibroblasts from Microalbuminuric Patients with Non-Insulin-Dependent Diabetes Mellitus

1996 ◽  
Vol 91 (6) ◽  
pp. 703-710 ◽  
Author(s):  
R. Trevisan ◽  
E. Duner ◽  
M. R. Cipollina ◽  
F. Di Virgilio ◽  
M. Trevisan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Angiotensin Ii ◽  
Intracellular Ph ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Intracellular Free Calcium ◽  
Dependent Diabetes Mellitus ◽  
Free Calcium ◽  
Control Subjects ◽  
Insulin Dependent

1. Whether an alteration in cell membrane cation transport after exposure to insulin and angiotensin II (two important growth promoters that have been shown to be involved in the pathogenesis of atherosclerosis and hypertension) is present in cells from non-insulin-dependent diabetes patients with microalbuminuria, a known risk factor for cardiovascular and renal disease, is unknown. We therefore examined intracellular pH and calcium changes after acute exposure to insulin and angiotensin II in cultured skin fibroblasts from eight non-insulin-dependent diabetes patients with and eight others without microalbuminuria and from a group of seven matched, normal control subjects. 2. Cultured fibroblasts were loaded with 2′,7′-bis (2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester or fura 2-acetoxymethyl ester for continuous monitoring of intracellular pH and free calcium concentrations respectively. 3. In quiescent growth-arrested cells, both intracellular pH and free calcium concentrations were similar in the three groups of subjects. Acutely, insulin induced a gradual alkalinization in all groups of patients. The pH increase was significantly greater in non-insulin-dependent diabetes mellitus patients with microalbuminuria (ΔpH +0.24 ± 0.04 pH units) than in normoalbuminuric patients with non-insulin-dependent diabetes mellitus (0.08 ± 0.02; P < 0.01) and normal control subjects (0.05 ± 0.01; P < 0.01). Although the alkalinizing effect of angiotensin II was smaller than that obtained by insulin, intracellular pH increase after angiotensin addition was more pronounced in non-insulin-dependent diabetes mellitus patients with microalbuminuria (ΔpH ± 0.14 ± 0.04 pH units) than in those without (0.08 ± 0.02; P < 0.01) and in normal control subjects (0.02 ± 0.02; P < 0.01). That the increase in intracellular pH was mediated by the sodium—hydrogen antiport was demonstrated by its dependence on the presence of sodium in the medium and its inhibition by amiloride. Whereas insulin addition did not evoke any significant increase in intracellular free calcium levels in fibroblasts from the three groups studied, angiotensin II evoked a fast and transient rise in intracellular free calcium that was higher in fibroblasts from microalbuminuric patients with non-insulin-dependent diabetes mellitus than in cells from normoalbuminuric patients with non-insulin-dependent diabetes mellitus and control subjects. In the whole population of patients with non-insulin-dependent diabetes mellitus, the increase in intracellular pH after exposure to angiotensin II was positively correlated with intracellular free calcium increase (r = 0.53; P < 0.05), suggesting a possible role of intracellular free calcium levels in the activation of the sodium—hydrogen antiport. 4. In conclusion, we have described an association between increased agonist-induced responsiveness of sodium—hydrogen antiport activity and the presence of microalbuminuria in patients with non-insulin-dependent diabetes mellitus. This increased responsiveness, persisting in cultured fibroblasts after several passages in vitro, suggests that in vitro phenotypic characteristics of fibroblasts are likely to be genetically determined and to be, at least in part, independent of the degree of metabolic control in vivo.

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