It is demonstrated that carboxypeptidase Y can be used to exchange the C-terminal alanyl residue of porcine insulin with a threonyl residue, thus forming human insulin. Using threonine amide as nucleophile, the reaction proceeds as a transpeptidation via human insulin amide, des(Ala)a30(Thr-NH2)a30insulin. However, since the amidase activity of carboxypeptidase Y towards this particular insulin...

For the past 30 years, data have suggested that unique islet populations exist, based on morphology and glucose sensitivity. Yet little has been done to determine the mechanism of these functional differences. The purpose of this study was to determine whether human islets were comprised functionally unique populations, and to elucidate a possible mechanism. Islets or pancreatic sections from 2...

BACKGROUND In order to enhance the absorption of insulin following subcutaneous injection, excipients were selected to hasten the dissociation rate of insulin hexamers and reduce their tendency to reassociate postinjection. A novel formulation of recombinant human insulin containing citrate and disodium ethylenediaminetetraacetic acid (EDTA) has been tested in clinic and has a very rapid onset ...

The guinea pig is an alternate small animal model for the study of metabolism, including insulin sensitivity. However, only one study to date has reported the use of the hyperinsulinemic euglycemic clamp in anesthetized animals in this species, and the dose response has not been reported. We therefore characterized the dose-response curve for whole body glucose uptake using recombinant human in...

BACKGROUND Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while thei...

Insulin detemir is a novel human insulin analog that does not show the usual propensity for weight gain in diabetic patients. We speculated that this beneficial effect could be due to insulin detemir exerting stronger anorectic effects within the brain than other insulins. To study the central effects of regular human insulin and insulin detemir on food intake, the present study was undertaken....

Great improvements have been made to insulin preparations over the years, including the development of insulin analogs, which were designed to overcome the disadvantages of traditional human insulins in the treatment of type 1 and type 2 diabetes. Insulin analogs more closely mimic the physiological insulin profile and are therefore associated with an improved balance between glycemic control a...

Human-induced pluripotent stem cell- (iPSC-) derived insulin-producing cells (IPCs) can be used for islet cell transplantation into type 1 diabetic patients and as patient-specific the development of novel antidiabetic drugs. However, a method is needed to generate functional IPCs from iPSCs simplify protocol. We compared combinations small molecules that could induce differentiation definitive...