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Glucotoxicity Caused by Change in Hepatic Metabolic Pathways Leading to Type 2 Diabetes
Author(s) -
Kapuria Devika,
Herndon Betty,
Molteni Agostino
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.767.1
Subject(s) - type 2 diabetes , diabetes mellitus , medicine , endocrinology
Recent reviews emphasize type 2 diabetes initiation by chronic liver exposure to lipotoxicity and glucotoxicity by adding to the deterioration of glucose maintenance which characterizes type 2 diabetes. To investigate the interaction of these contributing factors, we utilized 4 groups (10 each) of OB/OB mice: Grp 1 received a normal diet (Harlan Teklad); Grp 2 received the same diet with all methionine and choline lacking (MCD diet, same % CHO, protein, fat). Grp 3 was the normal diet with a high clinical dose of Ω3‐fatty acids, grp 4 received the MCD diet with the same dose of Ω3‐fatty acids as group 3. Hypothesis The MCD diet for 2 months would change liver lipid and fatty acid composition, while Ω3‐fatty acid feeding would change steatosis. The OB/OB mice (leptin k/o) have high food intake which aids glucose desensitization. Together the metabolic picture emulates type 2 diabetes. At 2 weeks, half of group 3 died suddenly , Leptin receptor analysis was normal. At 2 months, necropsies on all others showed >600 blood glucose in most grp 4 survivors with significantly depressed hepatic glycogen. Image J analysis was performed to quantitatively estimate the percentage of glycogen in the study groups. Grp 1 had a glycogen content of 17.55 % (±3.724), grp 2 20.53 (±6.25), grp 3 11.8 (±2.95) and grp 4 19.809 (±7.75). Analysis of insulin showed elevated levels in the hyperglycemic mice in grp 3 as compared to the normoglycemic mice in grp 4. Beta cells of pancreas in these animals showed minimal inflammation. These data demonstrate an important input of hepatic metabolic pathways on the glucotoxity and lipotoxicity that may define type 2 diabetes.