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Ketogenic diets increase hepatic insulin resistance by the attenuation of hypothalamic leptin signaling and hepatic insulin signaling in diabetic rats
Author(s) -
Park Sunmin,
Hong Sang Mee,
Ahn Il Sung
Publication year - 2009
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.23.1_supplement.541.5
Subject(s) - medicine , endocrinology , insulin resistance , insulin , ampk , glucagon , tyrosine phosphorylation , glucose clamp technique , phosphorylation , pancreatic hormone , chemistry , protein kinase a , receptor , biochemistry
We determined the effects of ketogenic diet (KTD) on insulin resistance and insulin secretion in 90% pancreatectomized (Px) diabetic rats. KTD (0 En% carbohydrates and 78 En% fat) or control diet (COD; 58 En% carbohydrates and 20 En% fat) was given to diabetic rats for 4 weeks. Serum glucagon and leptin levels were higher in rats fed KTD (p<0.05). During oral glucose tolerance test, serum glucose levels slowly increased until 80 min in KTD, compared to COD, and they decreased slowly. Insulin secretion capacity at hyperglycemic clamp did not significantly differ between two groups. However, euglycemic hyperinsulinemic clamp revealed KTD decreased glucose infusion rates and increased hepatic glucose output at hyperinsulinemic states. KTD attenuated hypothalamic STAT‐3 phosphorylation in comparison with the control diet. The increased hepatic glucose output in KTD was associated with increased hepatic PEPCK expression through attenuated tyrosine phosphorylation of IRS2 and serine473 phosphporylation of Akt (p<0.05). Additionally, hepatic serine phosphorylation of AMPK and ACC was reduced in KTD (p<0.05), suggesting decreased fatty acid oxidation and decreased triglyceride synthesis. In conclusion, KTD suppressed hepatic insulin sensitivity through attenuated AMPK phosphorylation and insulin signaling in diabetic rats.