The influence of lactate on human adipocytes lipolysis and the possible relationship between lactate-induced metabolic effects and beta-adrenoceptor binding sites were investigated. beta-sites were identified in membranes with (125I)-cyanopindolol and in intact cells with (125I)-cyanopindolol and (3H)-CGP 12177. Lactate reduced isoproterenol-induced lipolysis in a dose-response fashion and such inhibition became significant only at 16 mmol/l lactate. Exposure of human fat cells to 16 mmol/l lactate significantly reduced beta-adrenoceptors density on crude membranes. When the binding assay was performed on intact cells using (125I)-cyanopindolol at 37 degrees C, the radioligand identified the same number of receptors, regardless of the presence of lactate in the preincubation medium. When (3H)-CGP 12177 was used, it bound to about 35% less receptors in lactate pre-treated cells than in control. Seemingly, at 37 degrees C, because of its lipophilicity, (125I)-cyanopindolol can cross the plasma membrane and bind to intracellular sites whereas, (3H)-CGP 1277, due to its hydrophilicity, identifies surface receptors only. Thus, the present in vitro study provides evidence that high levels of lactate, similar to the concentrations usually achieved in overt lactic acidosis, are able per se to inhibit human lipolysis and to redistribute beta-adrenoceptors from cell surface to a domain not accessible to hydrophilic ligands.

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In the present study we evaluated somatomedin-C (Sm-C) plasma levels in diabetic patients, with and without retinopathy. One hundred and thirty four diabetic patients (65 type I and 69 type II) and 90 controls, strictly matched for age and sex, were enrolled in the study. Ophthalmoscopy and fluorescein angiography allowed to distinguish: 49 patients without retinopathy, 45 patients with background retinopathy, and 40 with proliferative retinopathy. Growth hormone (GH) and Sm-C plasma levels were measured using a pool of 20-24 blood samples over 24h. Sm-C levels in type I (0.62 +/- 0.11 U/ml) and type II (0.56 +/- 0.09 U/ml) patients were significantly decreased (p less than 0.01) when compared to controls (0.89 +/- 0.30 U/ml). The mean daily secretion of GH was significantly (p less than 0.01) greater in diabetic patients (7.8 +/- 2.6 ng/ml) than in controls (4.1 +/- 1.5 ng/ml), but no correlation was found between Sm-C and GH (r = 0.15; p = n.s.). Our findings did not show any correlation between Sm-C plasma levels and either the existence of retinopathy, regardless of the degree of microvascular damage, or duration of the disease, or degree of metabolic control, as evaluated by HbA1c.

Optimal and early control of recent onset, type I diabetes by intensive insulin therapy has been reported to allow insulin withdrawal in about two thirds of subjects treated. We used continuous s.c. insulin infusion (CSII) in the attempt to induce a temporary remission of insulin dependence in 18 newly diagnosed young adult diabetics. After 10 days of optimized glycometabolic control, insulin infusion was stopped and patients were switched to glibenclamide (15 mg/die) plus metformin (1 g/die). Diabetics were considered in remission of insulin dependence when their metabolic control fulfilled the following criteria for at least 3 months: absence of glycosuria, pre- and post-prandial blood glucose less than or equal to 120 and 180 mg/dl, respectively, HbA1c less than or equal to 7%. Insulin therapy could be discontinued for periods of over three months in 11 subjects (61%) and for as long as 18 months in one case. Insulin requirement during CSII was slightly higher in nonremitters (NR) than in remitters (R): 0.36-0.64 vs 0.26-0.41 U/kg/die. After 24 months from CSII, R still showed lower insulin requirement (0.35-0.42 U/kg/die) than NR (0.55-0.75 U/kg/die). Further, the role of some hormonal and immunologic factors was investigated. Plasma C-peptide and glucagon were measured, fasting and 2h after each meal, both on admission and immediately after CSII, when patients were switched to oral therapy. No difference in hormone levels could be detected on admission, whereas, after CSII, mean post-prandial increase of C-peptide over basal was significantly higher in R than in NR (1.18 +/- 0.37 vs 0.22 +/- 0.16 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)