Identification of seven loci for static glucokinesis and dynamic glucokinesis in mice

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by a breakdown of glucose homeostasis and is responsible for serious complications in various organs and vessels. Most of the genetic factors of NIDDM are yet unknown. Here, we identified two types of genetic factors that regulate homeostasis of blood glucose by measuring various pharmacokinetic parameters, some of which are used in the non-compartment analysis of drug metabolism in 340 F₂ progeny from the NIDDM model KK-A^y/Ta Jcl mouse strain, and in non-diabetic PWK strain. We define ``static glucokinesis' as the regulation of homeostasis that occurs during glucose deprivation, and ``dynamic glucokinesis' as that during glucose stress; for instance, glucose tolerance test. Quantitative trait locus analysis revealed eight loci involved in the regulation of glucose homeostasis on chromosomes 7 (Nidd1k), 2 (Nidd2k), 1 (Nidd3k, Nidd4k, and Nidd5k), 11 (Nidd6k), 5 (Nidd7k) (named Nidd1k through Nidd7k), and 4 (Bwt1k). Nidd1k, Nidd4k, and Nidd7k were novel loci associated with NIDDM in mice. Nidd1k, Nidd2k, Nidd3k, and Nidd4k had linkage to factors characteristic of both static and dynamic glucokinesis. Nidd5k and Nidd6k showed linkage specific to markers of dynamic glucokinesis, and Nidd7k had linkage specific to static glucokinesis. Bwt1k was linked to obesity. Thus, the genetic factors for static glucokinesis and those for dynamic glucokinesis partially overlapped.