Obesity, insulin resistance, and metabolic syndrome: a study in WNIN/Ob rats from a pancreatic perspective.
Alterations in pancreatic milieu to adapt to physiological shifts occurring in conditions of obesity and metabolic syndrome (MS) have been documented, though mechanisms leading to such a state have remained elusive so far. The data presented here tries to look at the gravity of metabolic insult during the early and prolonged phases of obesity/insulin resistance (IR) depicted in WNIN/Ob strain of rats-an obese euglycemic mutant rat model developed indigenously at our institute which is highly vulnerable for a variety of degenerative diseases. The present results in situ show the participation of several confounding factors in the pancreatic milieu that collectively coprecipitates for a state of profound inflammation in the pancreas (among Mutant compared to Lean/Control) which gets worsened with age. These include hypertrophy, macrophage infiltration (CD11b/TNFα/IL6), apoptosis, β-cell vacuolation, hyperinsulinemia (HI), and stress markers (RL-77/HSP104/TBARS) all of which correlated well with indices for obesity (2-3 fold), IR (1.5-3 fold), and HI (2-3 fold). Further, supportive data was also obtained from in vitro studies using islet cell cultures amongst phenotypes. Taken together, these results advocate that inflammation was the major precipitating factor to cause islet cell dysfunctions (in situ and in vitro) in these Mutant rats compared to their Lean littermates and parental Control.
Department of Biochemistry/Stem Cell Research, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania (P.O), Hyderabad, Andhra Pradesh 500007, India.
Vijayalakshmi
V
Venkatesan
Department of Biochemistry/Stem Cell Research, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania (P.O), Hyderabad, Andhra Pradesh 500007, India.
Soundarya L
SL
Madhira
Department of Biochemistry/Stem Cell Research, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania (P.O), Hyderabad, Andhra Pradesh 500007, India.
Venkata M
VM
Malakapalli
Department of Biochemistry/Stem Cell Research, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania (P.O), Hyderabad, Andhra Pradesh 500007, India.
Maniprabha
M
Chalasani
Department of Biochemistry/Stem Cell Research, National Institute of Nutrition, Indian Council of Medical Research, Jamai-Osmania (P.O), Hyderabad, Andhra Pradesh 500007, India.
Sarfaraz N
SN
Shaik
Laboratory 12, National Center for Cell Sciences, NCCS Complex, Pune University Campus, Ganeshkhind, Pune, Maharashtra 411007, India.
Vasudevan
V
Seshadri
Division of Community Studies, National Institute of Nutrition, Hyderabad, Andhra Pradesh 500007, India.
Venkaiah
V
Kodavalla
Manipal Institute of Regenerative Medicine, GKVK Post, Bellary Road, Allalasandra, Yelahanka, Bangalore, Karnataka 560065, India.
Ramesh R
RR
Bhonde
National Center for Laboratory Animal Sciences, National Institute of Nutrition, Hyderabad, Andhra Pradesh 500007, India.
Giridharan
G
Nappanveettil
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000096:biosynthesis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000473:pathology; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D061251:Primary Cell Culture; D051381:Rats; D015534:Trans-Activators / Q000096:biosynthesis
D001786:Blood Glucose; D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein