Norihiro Kato

Genistein augments cyclic adenosine 3'5'-monophosphate(cAMP) accumulation and insulin release in MIN6 cells.

Effects of genistein on insulin release were studied using MIN6 cells, a glucose-sensitive insulinoma cell line. At the non-stimulatory concentrations of glucose, genistein did not affect insulin release, however, at the stimulatory concentrations of glucose, genistein significantly increased insulin release in a dose-dependent manner up to 20 micrograms/ml. The content of cAMP in MIN6 cells was also elevated significantly by genistein and the dose-response relationship between the genistein and cAMP accumulation was consistent with the relationship between the genistein and insulin release. These effects were inhibited by calcium antagonists or by the omission of extracellular calcium. Isobutylmethylxanthine (IBMX;0.1mM) increased both cAMP accumulation and insulin release in MIN6 cells and there were no additive effects by the addition of genistein. The accumulation of cAMP might have, at least in part, resulted from phosphodiesterase inhibition by genistein. These results suggest that genistein augments glucose-induced insulin release by the contribution of cAMP accumulation and calcium modulation which depends on extracellular calcium.

The relationship between early diabetic nephropathy and control of plasma glucose in non-insulin-dependent diabetes mellitus: The effect of glycemic control on the development and progression of diabetic nephropathy in an 8-year follow-up study

To clarify the relationship between early diabetic nephropathy and the glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) without hypertension, excretion of urinary albumin was studied retrospectively for 8 years. The patients with early diabetic nephropathy were divided into two groups according to the initial urinary albumin index (UAI: mg/g.creatinine), namely, a normoalbuminuric (less than 15 mg/g.creatinine) and a microalbuminuric group (15 < or = UAI < 200 mg/g.creatinine). Comparisons of changes in UAI were made between good (HbA1 < 9.0% and fasting plasma glucose (FPG) < 140 mg/100 mL throughout the observation period) and poor glycemic control groups after 4 and 8 years. In the patients with normoalbuminuria at the initial determination, five of 11 patients (45.5%) with good glycemic control and 14 of 22 patients (63.6%) with poor glycemic control became microalbuminuric after 8 years, respectively (p < 0.05). In the microalbuminuric patients, five of ten patients (50%) with poor glycemic control became macroalbuminuric (UAI > or = 200 mg/g.creatinine), although only one case worsened of five patients with good glycemic control (p < 0.05). In conclusion, the development or progression of early diabetic nephropathy in NIDDM was significantly inhibited by good glycemic control (FPG < 140 mg/100 mL and HbA1 < 9.0%), independent of hypertension, and probably irrespective of the mode of therapeutic intervention.

Clinical implications of serum levels of basement membrane components in diabetic patients with and without albuminuria.

Serum levels of type IV collagen (7S-IV) and laminin P1 in 185 non-insulin-dependent diabetes mellitus patients were significantly higher than those in normal subjects. Furthermore, they were significantly elevated in relation to the excretion of urinary albumin, showing their increases even at the stage of microalbuminuria, although they were not correlated with HbA1c or age in diabetic patients. Thus, the determination of serum levels of basement membrane components, 7S-IV and laminin, could be beneficial as the early indices of diabetic microangiopathy, including diabetic nephropathy.

The role of insulin in coronary atherosclerosis

In 197 patients with coronary artery disease (CAD) who underwent coronary angiography, 75 g oral glucose tolerance test (OGTT) was performed, measuring plasma glucose(PG) and plasma insulin (IRI) at 4 time points (0, 30, 60 and 120 min). Subjects were separated into two groups by their insulinogenic index (I.I. = delta IRI/delta PG from 0 up to 30 min), 99 cases with good insulin response (I.I. > or = 0.4) and 98 cases with poor insulin response (I.I. < 0.4). Only two subjects were diabetic in good insulin response, while 37 were diabetic in poor insulin response. The severity of coronary atherosclerosis was expressed as a coronary index (CI), calculated according to Balcons method. Fasting PG and the sum of PG were significantly higher in the latter group, while the sum of IRI was significantly lower. CI was not significantly different, however. In the group with good insulin response, the severity of CAD was significantly correlated to fasting IRI (n = 99, r = -0.387, P < 0.02), but, there was no such relationship in the other group. We conclude that hyperinsulinemia might be a risk factor for ischemic heart disease, but in diabetics it is difficult to link the relationship between fasting IRI and CI.