Intravenous infusion of diarginylinsulin, an insulin analogue: effects on glucose turnover and lipid levels in insulin-treated type II diabetic patients.

Diarginylinsulin is an intermediate in the conversion of proinsulin to insulin and is usually present in small amounts in vivo in humans. This study was designed to evaluate the following in insulin-treated type II diabetic patients: (1) the feasibility of an overnight intravenous infusion of diarginylinsulin, as compared with an overnight intravenous infusion of short-acting insulin, and the degree of early morning glycemic control; and (2) the effects of diarginylinsulin and human insulin on hepatic glucose production (HGO) in the postabsorptive state and on the glucose turnover rate and peripheral insulin sensitivity during an euglycemic hyperinsulinemic clamp. Diarginylinsulin and regular human insulin maintained a comparable degree of normoglycemia during the night, without significant glucose increases in the morning.

Insulin delivery by implantable pumps.

We have developed a neutral human insulin (Hoe 21 GH) which is stabilized for use in implantable roller pumps. After extensive in vitro tests and animals experiments this preparation was selected for a clinical trial in humans. Twenty remote-controlled insulin pumps (Siemens AG) were implanted into insulin-dependent Type I diabetic patients for a one-year feasibility trial in four centres.

In vitro activity of biosynthetic human diarginylinsulin.

In diarginylinsulin two arginine residues are located at the C-terminal end of the B-chain (ArgB31 and ArgB32). This accounts for a shift of the isoelectric point from pH 5.4 in native insulin to pH 7.

Glycerol-insulin raises circulating insulin antibodies in type I diabetic patients treated with permanently implanted devices.

The instability of insulin in the reservoirs of implantable insulin delivery devices has been a major obstacle in implementing this form of therapy. To overcome the problem of precipitation, a glycerol-insulin preparation has been used in large-scale long-term clinical trials. The aim of this study was to evaluate the stability of the glycerol-insulin solution and its effects on circulating insulin antibodies in eight type I diabetic patients who were implanted with an Infusaid pump (Infusaid Corporation, Norwood, MA) and followed for 1 year or more.

Comparison of the effect of two different hypoglycemic agents, glibenclamide and HB 699, on the rat small intestinal absorption of sugars and amino acids.

4-(2-[5-Chloro-2-methoxy-benzamido]-ethyl)-benzoic acid (HB 699) belongs to the group of hypoglycemic benzoic acid derivatives. Although lacking the sulfonylurea group, the structure of HB 699 partly resembles that of glibenclamide which is known to impair small-intestinal glucose absorption in vitro at high concentrations. Whereas this intestinal effect of glibenclamide is unlikely to contribute to its blood-glucose lowering properties, extrapancreatic and particularly intestinal effects may be important for the antidiabetic action of HB 699.