Dogfish glucagon analogues counter hyperglycaemia and enhance both insulin secretion and action in diet-induced obese diabetic mice

Aims To investigate the antidiabetic actions of three dogfish glucagon peptide analogues [known glucagon‐like peptide‐1 and glucagon receptor co‐agonists] after chronic administration in diet‐induced high‐fat‐diet‐fed diabetic mice. Materials and methods National Institutes of Health Swiss mice were pre‐conditioned to a high‐fat diet (45% fat) for 100 days, and control mice were fed a normal diet (10% fat). Normal diet control and high‐fat‐fed control mice received twice‐daily intraperitoneal (i.p.) saline injections, while the high‐fat‐fed treatment groups (n = 8) received twice‐daily injections of exendin‐4(1‐39), [S2a]dogfish glucagon, [S2a]dogfish glucagon exendin‐4(31‐39) or [S2a]dogfish glucagon‐Lys30‐γ‐glutamyl‐PAL (25 nmol/kg body weight) for 51 days. Results After dogfish glucagon analogue treatment, there was a rapid and sustained decrease in non‐fasting blood glucose and an associated insulinotropic effect (analysis of variance, p