Role of atrial natriuretic peptide (ANP) in the regulation of insulin secretion and vitality of pancreatic ß cells

genotype-independent increase in body weight, arterial blood pressure and fasted blood glucose levels. Moreover, all mice showed a pathological oral glucose tolerance test (oGTT), confirming an insulin resistant state. In control mice, immunostainings of insulin and morphometrical analyses showed an increase in the islet area, the total area of s cells per islet and in the number of s cells per islet after HFD. Since the area of single s cells remained the same under ND and HFD, these results demonstrate that the observed increase in s cell mass was caused by s cell proliferation and not by hypertrophy. Strikingly, s cell proliferation in response to HFD-provoked insulin resistance was abolished in s GC-A KO mice. As mentioned above, low plasma levels of ANP predict development of future diabetes and glucose progression in the elderly, suggesting a (co)causal role of deficient ANP/ GC-A signalling in diabetes development [2]. To study whether chronic s cell ANP/GC-A dysfunction alters insulin-dependent glucose homeostasis, we analyzed female s GC-A KO and control mice at 10-15 months of age. Fasted insulin plasma levels were not different between genotypes. Surprisingly, the oGTT showed a better glucose handling in the s GC-A KO mice, with lower plasma glucose levels at all time-points and a significantly lower area under the curve (AUC). Insulin sensitivity was not different between genotypes. However, glucose-stimulated insulin release was enhanced in the s GC-A KO mice.