Effects of glibenclamide on serum lipids, lipoproteins, thromboxane, beta-thromboglobulin, and prostacyclin in non-insulin-dependent diabetes mellitus.

A study was conducted to determine the effects of glibenclamide on serum lipoproteins, apolipoproteins, thromboxane (TXA2), prostacyclin (PGI2), and beta-thromboglobulin (B-TGL) in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). In 20 NIDDM patients, aged 34 to 67 (mean, 53.6) years, without clinical signs of atherosclerotic disease and whose blood sugar level was over 140 mg/dl after four weeks of dietary treatment, fasting blood samples were taken before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glibenclamide treatment. Pretrial levels of total serum cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in the diabetic patients did not differ from those in nondiabetic controls, whereas high-density lipoprotein cholesterol (HDL-C) levels and the percentage of TC bound to HDL (HDL-C%) were significantly lower in the patients than in controls. After combined dietary and glibenclamide treatment and the normalization of blood sugar, both HDL-C (mg/dl) levels and HDL-C% levels increased significantly. TC, TG, and LDL-C levels decreased. Levels of apolipoproteins A1 and A2 rose and apolipoprotein B fell, but differences were not significant. TXB2 and 6-keto-PGF1-alpha (the inert metabolites of TXA2 and PGI2) and B-TGL were determined by radioimmunoassay. TXB2 and B-TGL levels decreased significantly after glibenclamide administration, indicating attenuation of platelet aggregation. No changes in PGI2 were observed. The results demonstrate the favorable effect of glibenclamide on lipoproteins and apolipoproteins in NIDDM patients, especially in increasing HDL-C levels and HDL-C%, and in attenuating platelet aggregation as indicated by reduction of TXB2 and B-TGL.

Effects of glyburide treatment on serum lipoprotein and apolipoprotein concentrations and ratios in non-insulin-dependent diabetes mellitus.

Lipoproteins and apolipoproteins were studied in 28 patients with newly detected non-insulin-dependent diabetes mellitus (NIDDM) before and after combined dietary and glyburide treatment. The patients, aged 33 to 67 years and without coronary or other atherosclerotic diseases, displayed fasting blood sugar levels of over 140 mg/dl after four weeks of dietary treatment. Overnight fasting blood samples were collected before the beginning of the trial, after four weeks of dietary treatment, and after four and eight weeks of combined dietary and glyburide treatment. The pretrial levels of total serum cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 and A2, and apolipoprotein B were similar to or even lower than those of nondiabetics; however, high-density lipoprotein cholesterol (HDL-C) levels and HDL-C% (the percentage of TC bound to HDL) were significantly lower in the diabetic patients. After combined dietary and glyburide treatment and normalization of blood sugar, apolipoprotein A1 and A2, HDL-C levels, and HDL-C% increased significantly. TC, TG, and LDL-C levels, although not exceeding the normal range, decreased significantly. HDL-C2 and HDL-C3 levels also increased, but the differences did not reach significance. Among the lipid, lipoprotein, and apolipoprotein ratios in the patients, only the ratios HDL-C:LDL-C, apolipoprotein A1:apolipoprotein B, and HDL-C: apolipoprotein B increased significantly as a result of the opposing responses of the protective lipoprotein HDL-C and apolipoprotein A1 and the atherogenic lipoprotein LDL-C and apolipoprotein B. The results demonstrate the favorable effects of combined dietary and sulphonylurea drug treatment on lipoproteins and apolipoproteins in NIDDM patients, thereby reducing coronary and atherosclerotic risks.

Potentiation by previous nutrients of glibenclamide-induced insulin release in man. An effect which is counteracted by meal-induced retardation of drug absorption.

We have studied the impact of a previous meal on insulin and glucose responses to the subsequent administration of glibenclamide. Healthy volunteers and NIDDM patients ingested a standard low-carbohydrate breakfast, and glibenclamide was administered 110-120 min later either as an intravenous bolus (12.5 micrograms/kg body wt), or as a tablet (5 mg HB 419). When glibenclamide was administered i.v. the drug raised insulin and lowered blood glucose levels, and previous breakfast potentiated these effects both in healthy volunteers and in NIDDM patients. Conversely when glibenclamide was given as a tablet the drug per se raised C-peptide and lowered blood glucose levels under fasting conditions, whereas the drug had no effect when ingested after breakfast. Measurements of glibenclamide in plasma revealed that previous breakfast delayed the systemic appearance of ingested glibenclamide. We conclude that nutrients sensitize insulin-releasing cells to subsequent stimulation by glibenclamide, thereby aggravate a blood-glucose-lowering effect of the drug. However this effect, which could potentially induce undesirable hypoglycaemia in sulphonylurea-treated diabetics, is counteracted when glibenclamide is taken orally because of a meal-induced decrease in drug absorption.

Increase in circulating basement membrane antigens in diabetic rats and effects of insulin treatment.

The serum concentrations of two recently discovered antigens derived from basement membranes (7-S collagen and laminin P2) were assayed in streptozotocin-diabetic rats as possible indicators of basement membrane metabolism. The concentrations of both increased significantly after 8 weeks of diabetes, and that of 7-S collagen at least remained elevated up to 24 weeks. Treatment with insulin, which did not correct the metabolic disturbances, inhibited the increase in the concentration of 7-S collagen in serum, but did not completely normalize that of laminin P2.

[Insulin analogues with substitution of A1-glycine by D-amino acids and omega-amino acids (author's transl)]. / Insulinanaloga durch Austausch von A1-Glycin gegen D-Aminosäuren und omega-Aminosäuren.

Substitution of A1-glycine of insulin by L-amino acids yields in analogues with low biological activity. With D-amino acids in A1 biological activity is essentially retained. The influence of aliphatic, aromatic, acidic and basic alpha-D-amino acids as well as omega-amino acids in A1 on the biological effects in different test systems is studied and discussed.

[Acylaminoalkyl substituted benzoic and phenylalkane acids with hypoglycaemic properties (author's transl)]. / Acylaminoalkyl-substituierte Benzoe- und Phenylalkansäuren mit blutglukose-senkender Wirkung. Kurze Mitteilung.

Newly developed carbonic acids with hypoglycaemic properties are presented. Their activity is based on an insulin secretion with unusual biphasic dynamics which is seen both after enteral and parenteral administration. In vitro, the substances described have an inhibitory effect on gluconeogenesis in the liver and lipolysis in adipose tissue.

[(A1-beta-Alanine) insulin]. / [A1-beta-Alanin]Insulin

Starting from porcine insulin, A1-glycine was substituted by beta-alanine. The blood sugar lowering effect of the new analogue in the rabbit is about 45% of that of insulin. The half-maximal binding to partially purified rat liver receptors is about 46%, to transformed human lymphocytes about 54%, compared to insulin.

Trypsin-sensitive photosynthetic activities in chloroplast membranes from Chlamydomonas reinhardi, y-1.

Location of electron transport chain components in chloroplast membranes of chlamydomonas reinhardi, y-1 was investigated by use of proteolytic digestion with soluble or insolubilized trypsin. Digestion of intact membrane vesicles with soluble trypsin inactivates the water-splitting system, the 3-(3,4-dichlorophenyl)-1,1-dimethylurea inhibition site of Photosystem II, the electron transport between the two photosystems as well as the ferredoxin NADP reductase. Reduction of NADP with artificial electron donors for Photosystem I could be restored, however, by addition of purified reductase to trypsin-digested membranes. Electron transfer activities of Photosystems I and II reaction centers were resistant to trypsin digestion either from outside or from within the thylakoids when active trypsin was trapped inside the membrane vesicles by sonication and digestion carried out in the presence of trypsin inhibitor added from outside. In the latter case, the water-splitting system was also found to be resistant to digestion. Polyacrylamide-bound insolubilized trypsin inactivated only the ferredoxin NADP reductase. Photosynthetically active membranes obtained at different stages of development showed a basically similar behavior toward trypsin.

On a water soluble factor neutralizing antibodies against the primary acceptor in photosynthetic electron transport of chloroplasts.

Rabbits immunized against the thylakoid system of chloroplasts form two different antibodies against the reducing site of photosystem I. One inhibits photosynthetic NADP(+) and ferredoxin dependent cytochrome c reduction, but not photosynthetic anthraquinone reduction by isolated spinach chloroplasts. The other inhibits all three reductions. Both do not inhibit a Hill reaction with ferricyanide. The presumed antigen moiety against these antibodies was isolated as a water soluble factor released from lyophilized chloroplasts after treatment with diethylether. The heat stable, nondialysable factor has absorption peaks at 262 and 315 mµ. It is autoxidizable and has the property of a cytochrome c reducing substance. The factor neutralizes the antibody inhibition of photosynthetic anthraquinone and ferredoxin reduction. It is proposed that the soluble factor is the prosthetic group of the primary acceptor of photosystem I.