Pank1 deletion in leptin-deficient mice reduces hyperglycaemia and hyperinsulinaemia and modifies global metabolism without affecting insulin resistance.

ABSTRACT:

Aims/hypothesis

Pantothenate kinase (PANK) is the first enzyme in CoA biosynthesis. Pank1-deficient mice have 40% lower liver CoA and fasting hypoglycaemia, which results from reduced gluconeogenesis. Single-nucleotide polymorphisms in the human PANK1 gene are associated with insulin levels, suggesting a link between CoA and insulin homeostasis. We determined whether Pank1 deficiency (1) modified insulin levels, (2) ameliorated hyperglycaemia and hyperinsulinaemia, and (3) improved acute glucose and insulin tolerance of leptin (Lep)-deficient mice.

Methods

Serum insulin and responses to glucose and insulin tolerance tests were determined in Pank1-deficient mice. Levels of CoA and regulating enzymes were measured in liver and skeletal muscle of Lep-deficient mice. Double Pank

SUBMITTER: Leonardi R 

PROVIDER: S-EPMC4618598 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature