Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase Cα expression

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Abstract

Undernutrition has been shown to affect the autonomic nervous system, leading to permanent alterations in insulin secretion. To understand these interactions better, we investigated the effects of carbamylcholine (CCh) and phorbol 12-myristate 13-acetate (PMA) on insulin secretion in pancreatic islets from rats fed a normal (17%; NP) or low (6%; LP) protein diet for 8 wk. Isolated islets were incubated for 1 h in Krebs-bicarbonate solution containing 8.3 mmol glucose/L, with or without PMA (400 nmol/L) and CCh. Increasing concentrations of CCh (0.1-1000 μmol/L) dose dependently increased insulin secretion by islets from both groups of rats. However, insulin secretion by islets from rats fed the NP diet was significantly higher than that of rats fed the LP diet, and the dose-response curve to CCh was shifted to the right in islets from rats fed LP with a 50% effective concentration (EC50) of 2.15 ± 0.7 and 4.64 ± 0.1 μmol CCh/L in islets of rats fed NP and LP diets, respectively (P < 0.05). PMA-induced insulin secretion was higher in islets of rats fed NP compared with those fed LP. Western blotting revealed that the protein kinase (PK)Cα and phospholipase (PL)Cβ1 contents of islets of rats fed LP were 30% lower than those of islets of rats fed NP (P < 0.05). In addition, PKCα mRNA expression was reduced by 50% in islets from rats fed LP. In conclusion, a reduced expression of PKCα and PLCβ1, may be involved in the decreased insulin secretion by islets from LP rats after stimulation with CCh and PMA.

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Ferreira, F., Filiputti, E., Arantes, V. C., Stoppiglia, L. F., Araújo, E. P., Delghingaro-Augusto, V., … Carneiro, E. M. (2003). Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase Cα expression. Journal of Nutrition, 133(3), 695–699. https://doi.org/10.1093/jn/133.3.695

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