title: Vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating peptide receptor 2 deficiency in mice results in growth retardation and increased basal metabolic rate.
abstract: Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are two closely related peptides that bind two homologous G protein-coupled receptors, VIP/PACAP receptor 1 (VPAC1R) and VIP/PACAP receptor II (VPAC2R), with equally high affinity. Recent reports suggest that VPAC2R plays a role in circadian rhythm and T cell functions. To further elucidate the functional activities of VPAC2R, we generated VPAC2R-deficient mice by deleting exons VIII-X of the VPAC2R gene. The VPAC2R-deficient mice showed retarded growth and had reduced serum IGF-I levels compared with gender-matched, wild-type siblings. The mutant mice appeared healthy and fertile at a young adult age. However, older male mutant mice exhibited diffuse seminiferous tubular degeneration with hypospermia and reduced fertility rate. The mutant mice appeared to have an increase in insulin sensitivity. VPAC2R-deficient mice had increased lean mass and decreased fat mass with reduced serum leptin levels. Indirect calorimetry experiments showed that the respiratory quotient values immediately following the transition into the dark cycle were significantly higher in male knockout mice for about 4 h. Additionally, male and female VPAC2R-deficient mice presented an increased basal metabolic rate (23% and 10%, respectively) compared with their wild-type siblings. Our results suggest that VPAC2R plays an important role in growth, basal energy expenditure, and male reproductive functions.
authors.affiliation: Division of Endocrine Research, Eli Lilly and Co., Indianapolis, Indiana 46285, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Asnicar
authors.forename: Anja
authors.initials: A
authors.lastname: Köster
authors.forename: Mark L
authors.initials: ML
authors.lastname: Heiman
authors.forename: Frank
authors.initials: F
authors.lastname: Tinsley
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Smith
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Galbreath
authors.forename: Niles
authors.initials: N
authors.lastname: Fox
authors.forename: Yanfei Linda
authors.initials: YL
authors.lastname: Ma
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.forename: Hansen M
authors.initials: HM
authors.lastname: Hsiung
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001481:Basal Metabolism / Q000502:physiology*; D001823:Body Composition; D005260:Female; D006128:Growth / Q000502:physiology*; D006130:Growth Disorders / Q000235:genetics; D007248:Infertility, Male / Q000235:genetics; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008969:Molecular Sequence Data; D018005:Receptors, Vasoactive Intestinal Peptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D012016:Reference Values; D012671:Seminiferous Tubules / Q000473:pathology; D012727:Sex Characteristics; D013076:Sperm Count
chemical_list: D007328:Insulin; D020738:Leptin; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D007334:Insulin-Like Growth Factor I