High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress

M. Balakumar, Raji Rajesh Lenin, D. Prabhu, C. Sathishkumar, P. Prabu, V. Mohan, M. Balasubramanyam

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In the context of high human consumption of fructose diets, there is an imperative need to understand how dietary fructose intake influence cellular and molecular mechanisms and thereby affect β-cell dysfunction and insulin resistance. While evidence exists for a relationship between high-fat-induced insulin resistance and metabolic disorders, there is lack of studies in relation to high-fructose diet. Therefore, we attempted to study the effect of different diets viz., high-fat diet (HFD), high-fructose diet (HFS), and a combination (HFS + HFD) diet on glucose homeostasis and insulin sensitivity in male Wistar rats compared to control animals fed with normal pellet diet. Investigations include oral glucose tolerance test, insulin tolerance test, histopathology by H&E and Masson’s trichrome staining, mRNA expression by real-time PCR, protein expression by Western blot, and caspase-3 activity by colorimetry. Rats subjected to high-fat/fructose diets became glucose intolerant, insulin-resistant, and dyslipidemic. Compared to control animals, rats subjected to different combination of fat/fructose diets showed increased mRNA and protein expression of a battery of ER stress markers both in pancreas and liver. Transcription factors of β-cell function (INSIG1, SREBP1c and PDX1) as well as hepatic gluconeogenesis (FOXO1 and PEPCK) were adversely affected in diet-induced insulin-resistant rats. The convergence of chronic ER stress towards apoptosis in pancreas/liver was also indicated by increased levels of CHOP mRNA & increased activity of both JNK and Caspase-3 in rats subjected to high-fat/fructose diets. Our study exposes the experimental support in that high-fructose diet is equally detrimental in causing metabolic disorders.

Original languageEnglish (US)
Pages (from-to)93-104
Number of pages12
JournalMolecular and Cellular Biochemistry
Volume423
Issue number1-2
DOIs
StatePublished - Dec 1 2016

Fingerprint

Endoplasmic Reticulum Stress
High Fat Diet
Nutrition
Medical problems
Fructose
Insulin Resistance
Fats
Insulin
Diet
Liver
Rats
Messenger RNA
Pancreas
Glucose
Caspase 3
Colorimetry
Gluconeogenesis
Animals
Glucose Tolerance Test
Wistar Rats

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress. / Balakumar, M.; Rajesh Lenin, Raji; Prabhu, D.; Sathishkumar, C.; Prabu, P.; Mohan, V.; Balasubramanyam, M.

In: Molecular and Cellular Biochemistry, Vol. 423, No. 1-2, 01.12.2016, p. 93-104.

Research output: Contribution to journalArticle

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