Gestational protein restriction impairs glucose disposal in the gastrocnemius muscles of female rats

Chellakkan S. Blesson, Vijayakumar Chinnathambi, Sathish Kumar, Chandrasekhar Yallampalli

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Gestational low-protein (LP) diet causes hyperglycemia and insulin resistance in adult offspring, but the mechanism is not clearly understood. In this study, we explored the role of insulin signaling in gastrocnemius muscles of gestational LP-exposed female offspring. Pregnant rats were fed a control (20% protein) or an isocaloric LP (6%) diet from gestational day 4 until delivery. Normal diet was given to mothers after delivery and to pups after weaning until necropsy. Offspring were euthanized at 4 months, and gastrocnemius muscles were treated with insulin ex vivo for 30 minutes. Messenger RNA and protein levels of molecules involved in insulin signaling were assessed at 4 months. LP females were smaller at birth but showed rapid catchup growth by 4 weeks. Glucose tolerance test in LP offspring at 3 months showed elevated serum glucose levels (P<0.01; glycemia D area under the curve 342 ± 28 in LP vs 155 ± 23 in controls, mmol/L∗120 minutes) without any change in insulin levels. In gastrocnemius muscles, LP rats showed reduced tyrosine phosphorylation of insulin receptor substrate 1 upon insulin stimulation due to the overexpression of tyrosine phosphatase SHP-2, but serine phosphorylation was unaffected. Furthermore, insulin-induced phosphorylation of Akt, glycogen synthase kinase (GSK)-3a, and GSK-3b was diminished in LP rats, and they displayed an increased basal phosphorylation (inactive form) of glycogen synthase. Our study shows that gestational protein restriction causes peripheral insulin resistance by a series of phosphorylation defects in skeletal muscle in a mechanism involving insulin receptor substrate 1, SHP-2, Akt, GSK-3, and glycogen synthase causing dysfunctional GSK-3 signaling and increased stored glycogen, leading to distorted glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)756-767
Number of pages12
JournalEndocrinology
Volume158
Issue number4
DOIs
StatePublished - Apr 1 2017

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Skeletal Muscle
Glucose
Insulin
Phosphorylation
Proteins
Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Insulin Receptor Substrate Proteins
Glycogen Synthase
Protein-Restricted Diet
Tyrosine
Insulin Resistance
Muscle Proteins
Glucose Tolerance Test
Weaning
Glycogen
Phosphoric Monoester Hydrolases
Hyperglycemia
Vascular Resistance
Serine

ASJC Scopus subject areas

  • Endocrinology

Cite this

Gestational protein restriction impairs glucose disposal in the gastrocnemius muscles of female rats. / Blesson, Chellakkan S.; Chinnathambi, Vijayakumar; Kumar, Sathish; Yallampalli, Chandrasekhar.

In: Endocrinology, Vol. 158, No. 4, 01.04.2017, p. 756-767.

Research output: Contribution to journalArticle

Blesson, Chellakkan S. ; Chinnathambi, Vijayakumar ; Kumar, Sathish ; Yallampalli, Chandrasekhar. / Gestational protein restriction impairs glucose disposal in the gastrocnemius muscles of female rats. In: Endocrinology. 2017 ; Vol. 158, No. 4. pp. 756-767.
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