title: INSL5-deficient mice display an alteration in glucose homeostasis and an impaired fertility.
abstract: Insulin-like factor 5 (INSL5), a member of the insulin superfamily, is expressed in the colorectum and hypothalamus. To facilitate studies into the role of INSL5, we generated Insl5(-/-) mice by gene targeting. Insl5(-/-) mice were born in the expected Mendelian ratio, reached normal body weight, but displayed impaired male and female fertility that are due to marked reduction in sperm motility and irregular length of the estrous cycle. Furthermore, Insl5(-/-) mice showed impairment in glucose homeostasis with characteristic elevation of serum glucose levels at an advanced age. Glucose and insulin tolerance tests revealed that the increased blood glucose in Insl5(-/-) mice was due to glucose intolerance resulting from reduced insulin secretion. Morphometric and immunohistological analyses revealed that the Insl5(-/-) mice had markedly reduced average islets area and β-cell numbers. Furthermore, immunohistochemistry showed the expression of INSL5 in enteroendocrine cells in the colorectal epithelium and the presence of its putative receptor relaxin family peptide receptor 4 in pancreatic islet cells. These results suggest the potential role of INSL5 signaling in the regulation of insulin secretion and β-cell homeostasis.
authors: Institute of Human Genetics, Heinrich-Düker-Weg 12, D-37073 Göttingen, Germany. iadham@gwdg.de.
authors: Ozanna
authors: O
authors: Burnicka-Turek
authors: Belal A
authors: BA
authors: Mohamed
authors: Katayoon
authors: K
authors: Shirneshan
authors: Thatchawan
authors: T
authors: Thanasupawat
authors: Sabine
authors: S
authors: Hombach-Klonisch
authors: Thomas
authors: T
authors: Klonisch
authors: Ibrahim M
authors: IM
authors: Adham
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D030762:Estrous Cycle / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000235:genetics*; D007246:Infertility / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D036361:Peptide Hormones / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D013081:Sperm Motility / Q000235:genetics
chemical_list: C121388:Insl5 protein, mouse; D007328:Insulin; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D052216:Glucagon-Like Peptide 1; D005947:Glucose