Our data are in keeping with the hypothesis that simvastatin might be used as an additional means to preserve renal function in microalbuminuric hypercholesterolemic type 2 diabetic patients.

Our results clearly show for the first time that the reduction of blood pressure, together with 24 h urinary albumin excretion rate - two established cardiovascular risk factors, obtained during Simvastatin therapy in hypertensive type 2 diabetic patients - is in large part independent from the reduction of LDL Cholesterol.

Our results are consistent with the thesis that the Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is associated more often with the condition of high blood pressure than with normal blood pressure.

Non-insulin-dependent diabetes mellitus (NIDDM) is a multifactorial disorder, displaying heterogeneity both at the genotype and phenotype levels. It affects 3-8 % of the Caucasian population over 45 years [1,2]. The genetic susceptibility to NIDDM is likely to involve separate but interrelated functions (for example insulin secretion, insulin resistance, obesity, abdominal fat patterning, intermediary metabolism, etc.) which have clinical consequences as a result of environmental influence. The increased understanding of the physiology and molecular biology of NIDDM has led to the identification of a number of genes. Among different candidate genes investigated so far, a possible association between NIDDM and a Diabetologia (1997) 40: 89-94 Physiological and genetic characterization of the Gly40Ser mutation in the glucagon receptor gene in the Sardinian population Summary A Gly40Ser amino acid substitution in the glucagon receptor gene has been associated with non-insulin-dependent diabetes mellitus (NIDDM), but the questions raised about its physiological implications have not been resolved. The aim of this study was to determine the frequency of the Gly40Ser mutation in different regions of Sardinia and to investigate the physiological implications of the mutation in glucose and insulin homeostasis. We studied a population of 691 subjects, selected on the basis of their Sardinian origin. Only heterozygous subjects were found, 21 of 574 (3.6 %) in NIDDM patients and 5 of 117 in non-diabetic subjects (4.2 %). In northern Sardinia 3.4 % of the NIDDM patients were carriers of the Gly40Ser substitution, 1.4 % in central Sardinia, while 7.6 % carried the substitution in the Southern part. No significant differences were found between hypertensive and normotensive subjects with respect to the presence of Gly40Ser. Ten subjects with Gly40Ser were carefully matched for diabetic state, BMI, age, sex, and geographical origin with 10 patients with Gly40, and a glucagon infusion test was performed using 1, 3, 9 and 27 ng glucagon kg -1 ⋅ min -1 for 30 min. Blood for determination of glucose, glucagon, and insulin concentrations was drawn at 15-min intervals from the Controlateral arm. Plasma glucagon increased dose-dependently during the infusion with no significant difference between the two groups. Carriers of Gly40Ser had a significantly lower (p < 0.02) increase in plasma glucose concentration in response to glucagon infusion compared to Gly40 homozygous subjects at all times, while the plasma insulin increase was not significantly different at any time. In conclusion, our results indicate that the Gly40Ser variation is not associated with NIDDM in the Sardinian population, and that its frequency varies in different parts of Sardinia. Moreover in vivo Gly40Ser plays a physiological role in the glucose homeostasis under glucagon control both in NIDDM and non-diabetic subjects. This latter result suggests that this amino acid substitution in the glucagon receptor may lead to a decreased blood glucose concentration bec...

We report herein the effects of long-term intracerebroventricular (icv) dexamethasone in normotensive rats. Dexamethasone (0.002, 0.02, 0.2, and 2.0 micrograms/day) or its vehicle (0 microgram/day, n = 8 each group) was infused icv via subcutaneous miniosmotic pumps (Alzet 2002) for 24 days in male conscious Wistar rats (weight range 190-240 g). Eighteen Wistar rats (weight range 200-230 g) received either vehicle or dexamethasone (0.2 and 2 micrograms/day) subcutaneously (sc) for 24 days. Systolic blood pressure (SBP, tail cuff) and body weight were recorded two times a week in the trained conscious rats. Dexamethasone (0.2 micrograms/day icv) exerted a progressive significant decrease in SBP over 24 days compared with both rats receiving vehicle and to pretreatment values (108 +/- 4 vs. 122 +/- 4 and 120 +/- 2 mmHg, P < 0.01). As previously reported, a significant increase in SBP was observed after 6 days in rats given 2 micrograms/day sc dexamethasone compared with both rats receiving vehicle and to pretreatment values (150 +/- 4 vs. 122 +/- 2 and 120 +/- 2 mmHg, P < 0.01 for both). Thereafter, SBP remained at plateau for the entire experiment. A similar significant decrease in body weight gain with age was observed in rats given icv or sc dexamethasone. Our data suggest that the glucocorticoid receptors exert opposite effects on blood pressure when stimulated at the brain level instead of at the peripheral vascular level.