It has been largely established that low-density lipoprotein (LDL)-cholesterol level in E2 allele carriers (whether diabetic or not) was lower than in E2 non-carriers. The 2-fold increase of nephropathy in E2 non-carriers with NIDDM argues for a role for LDL in the development of human nephropathy in NIDDM patients. This result is in agreement with previous data established both in vitro and in vivo in animal models. These findings support evidence for the pathogenic and morphologic similarities between kidney disease and atherosclerosis in NIDDM patients.

Eight- to 12-amino acid long peptides, representing fragments of transforming growth factor-beta 1 (TGF beta 1) and TGF beta 2 were selected on the basis of their potential immunogenicity and were used to generate polyclonal antibodies. Anti-TGF beta 1-(91-103) antibodies recognized specifically TGF beta 1, prevented TGF beta 1 binding to NRK-49F cells, and neutralized the biological activity of TGF beta 1 in adrenocortical cells (consisting in the inhibition of angiotensin-II-induced cortisol production). Antibodies raised against TGF beta 2-(65-73) appeared to recognize TGF beta 2 with a better affinity than TGF beta 1, but were unable to block the binding of either TGF beta 1 or TGF beta 2 to their receptors or to inhibit their biological activity. These observations are in line with a prominant role of the C-terminal domain of TGF beta 1 in its interaction with its receptor(s) and, hence, in its biological activity. Using anti-TGF beta 1-(91-103) antibodies, we could localize immunoreactive TGF beta 1-like material in the cortex of adult bovine adrenal glands. No reactivity was detected in the capsule or adrenal medulla. The reactivity was maximal in the zona fasciculata/reticularis and weaker in the zona glomerulosa. TGF beta-like material was present in a latent form in the conditioned medium from primary cultures of bovine adrenocortical cells. These cells secreted about 5 ng heat-activatable TGF beta-like material/24 h of culture.10(6) cells. Taken together with our previous reports that bovine adrenocortical cells possess high affinity TGF beta 1 receptors and secrete a TGF beta 1-like molecule under a latent form, the present observations further support the hypothesis that TGF beta 1 or a closely immunologically related protein acts as an autocrine regulator of adrenocortical steroidogenic functions.

Lipid peroxidation is known to accelerate aging and microvascular lesions in diabetic patients. We studied the acute influence of improved glycemic control on the concentrations of plasma lipid peroxidation intermediates [malondialdehydes (MDA), organic hydroperoxides (OHP)] in ketotic insulin-dependent diabetic patients, as well as the interplay of enzymes such as glutathione peroxidase (GPX) and CuZn superoxide dismutase (CuZn-SOD), and trace elements (Zn, Se, Cu) postulated to be involved in free radical protection. These plasma components were measured on the first day of hospitalization (T0) and when the patient had attained a stable glycemic state after continuous insulin treatment (T1). Plasma MDA and OHP concentrations were high at the beginning of the study but approached reference values after glycemic equilibration. Plasma zinc concentrations were significantly (P < 0.05) decreased during the ketotic state, but also approached reference values with glycemic equilibration. Plasma selenium concentrations and GPX activity were relatively unchanged between T0 and T1. Erythrocyte GPX activity measured at T1 in six patients was below the reference values, whereas CuZn-SOD activity was not affected. Our results show that enhanced lipid peroxidation is associated with decreased zinc plasma concentrations in ketotic patients and underline the beneficial effects of continuous insulin infusion. The mechanisms involved are still unclear but may indicate the importance of extracellular zinc transfer secondary to glycemic disorders.

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