Impaired β-cell function in the adult offspring of rats fed a protein-restricted diet during lactation is associated with changes in muscarinic acetylcholine receptor subtypes. Issue 2 (28th January 2014)

• Record Type: Journal Article
• Authors: de Oliveira, Júlio C.; Miranda, Rosiane A.; Barella, Luiz F.; Torrezan, Rosana; Agostinho, Aryane R.; Ribeiro, Tatiane A. S.; Franco, Claudinéia C. S.; Malta, Ananda; Tófolo, Laize P.; Gravena, Clarice; Mathias, Paulo C. F.
• Is Part Of: British journal of nutrition. Volume 111:Issue 2(2014)
• Page Start: 227
• Page End: 235
• Publication Date: 2014-01-28
• Subjects: Nutrition -- Periodicals; 572.4
• DOI: 10.1017/S0007114513002213
• Languages: English
• ISSNs: 0007-1145

Abstract

<abstract abstract-type="normal"> <title> <x content-type="archive" xml:space="preserve">Abstract</x> </title> <p>Impaired pancreatic β-cell function, as observed in the cases of early nutrition disturbance, is a major hallmark of metabolic diseases arising in adulthood. In the present study, we aimed to investigate the function/composition of the muscarinic acetylcholine receptor (mAChR) subtypes, M<sub>2</sub> and M<sub>3</sub>, in the pancreatic islets of adult offspring of rats that were protein malnourished during lactation. Neonates were nursed by mothers that were fed either a low-protein (4 %, LP) or a normal-protein (23 %, NP) diet. Adult rats were pre-treated with anti-muscarinic drugs and subjected to the glucose tolerance test; the function and protein expression levels of M<sub>2</sub>mAChR and M<sub>3</sub>mAChR were determined. The LP rats were lean and hypoinsulinaemic. The selective M<sub>2</sub>mAChR antagonist methoctramine increased insulinaemia by 31 % in the NP rats and 155 % in the LP rats, and insulin secretion was increased by 32 % in the islets of the NP rats and 88 % in those of the LP rats. The selective M<sub>3</sub>mAChR antagonist 4-diphenylacetoxy-<italic>N</italic>-methylpiperidine methiodide decreased insulinaemia by 63 % in the NP rats and 40 % in the LP rats and reduced insulin release by 41 % in the islets of the NP rats and 28 % in those of the LP rats. The protein expression levels of M<sub>2</sub>mAChR and M<sub>3</sub>mAChR were 57 % higher and 53 % lower, respectively, in the islets of the LP rats than in those of the NP rats. The expression and functional compositions of M<sub>2</sub>mAChR and M<sub>3</sub>mAChR were altered in the islets of the LP rats, as a result of metabolic programming caused by the protein-restricted diet, which might be another possible effect involved in the weak insulin secretion ability of the islets of the programmed adult rats.</p> </abstract>