Gene deletion of inositol hexakisphosphate kinase 1 reveals inositol pyrophosphate regulation of insulin secretion, growth, and spermiogenesis.
Inositol pyrophosphates, also designated inositol diphosphates, possess high-energy beta-phosphates that can pyrophosphorylate proteins and regulate various cellular processes. They are formed by a family of inositol hexakisphosphate kinases (IP6Ks). We have created mice with a targeted deletion of IP6K1 in which production of inositol pyrophosphates is markedly diminished. Defects in the mutants indicate important roles for IP6K1 and inositol pyrophosphates in several physiological functions. Male mutant mice are sterile with defects in spermiogenesis. Mutant mice are smaller than wild-type despite normal food intake. The mutants display markedly lower circulating insulin.
Bhandari
Rashna
R
The Solomon H. Snyder Department of Neuroscience and Departments of Pharmacology and Molecular Sciences and Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Juluri
Krishna R
KR
Resnick
Adam C
AC
Snyder
Solomon H
SH
D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D007295:Inositol Phosphates / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis
D007295:Inositol Phosphates; D007328:Insulin; D017856:Phosphotransferases (Phosphate Group Acceptor); C099438:inositol hexakisphosphate kinase