Add time:08/12/2019         Source:sciencedirect.com

Metabolic potency of des-(B26–B30)-insulin-B25-amide, [TyrB25]des-(B26–B30)-insulin-B25-amide and [HisB25]des-(B26–B30)-insulin-B25-amide was studied in anaesthetized rats. Compared to insulin, full potency for des-(B26–B30)-insulin-B25-amide and an enhanced potency for both substituted analogues has been described previously on rat adipocytes in vitro. Hypoglycaemic effects following i.v. injection of all of these analogues were almost identical to those of native insulin with a half-maximal effective dose of ∼3 nmol · kg−1. Stimulation of glucose metabolism during euglycaemic hyper-insulin-/analogueaemic clamp studies was indistinguishable from that of the native hormone with a maximal stimulation of ∼19 mg · kg−1 · min−1 and half-maximal effective hormone concentrations of ∼1 pmol · ml−1. Analogue action on individual peripheral tissues estimated by the uptake of 2-deoxyglucose as well as stimulation of lipogenesis in epididymal fat was not different to that of insulin. These data demonstrate that C-terminal amidation of des-(B26–B30)-insulin results in a shortened molecule with full in vivo metabolic potency. When substituting phenylalanine in position B25 by tyrosine or histidine, the insulin-identical potency is preserved.

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