Gestational protein restriction impairs insulin regulated glucose transport mechanisms in gastrocnemius muscles of adult male offspring

Chellakkan S. Blesson, Kunju Sathishkumar, Vijayakumar Chinnathambi, Chandrasekhar Yallampalli

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Type II diabetes originates from various genetic and environmental factors. Recent studies showed that an adverse uterine environment such as that causedby a gestational low-protein (LP) diet can cause insulin resistance in adult offspring. The mechanism of insulin resistance induced by gestational protein restriction is not clearly understood. Our aim was to investigate the role of insulin signaling molecules in gastrocnemius muscles of gestational LP diet-exposed male offspring to understand their rolein LP-induced insulin resistance. Pregnant Wistarrats were fed a control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery and a normal diet after weaning. Only male offspring were used in this study. Glucose and insulin responses were assessed after a glucose tolerance test. mRNA and protein levels of molecules involved in insulin signaling were assessed at 4 months in gastrocnemius muscles. Muscles were incubated ex vivo with insulin to evaluate insulin-induced phosphorylation of insulin receptor (IR), Insulin receptor substrate-1, Akt, and AS160. LP diet-fed rats gained less weight than controls during pregnancy. Male pupsfrom LPdiet-fedmothers were smaller but exhibited catch-up growth. Plasma glucose and insulin levels were elevated in LP offspring when subjected to a glucose tolerance test; however, fasting levels were comparable. LP offspring showed increased expression of IR and AS160 in gastrocnemius muscles. Ex vivo treatment of muscles with insulin showed increased phosphorylation of IR (Tyr972) in controls, but LP rats showed higher basal phosphorylation. Phosphorylation of Insulin receptor substrate-1 (Tyr608, Tyr895, Ser307, and Ser318) and AS160 (Thr642) were defective in LP offspring. Further, glucose transporter type 4 translocation in LP offspring was also impaired. A gestational LP diet leads to insulin resistance in adult offspring by a mechanism involving inefficient insulin-induced IR, Insulin receptor substrate-1, and AS160 phosphorylation and impaired glucose transporter type 4 translocation.

Original languageEnglish (US)
Pages (from-to)3036-3046
Number of pages11
JournalEndocrinology
Volume155
Issue number8
DOIs
StatePublished - Aug 2014

ASJC Scopus subject areas

  • Endocrinology

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