title: Delta Cell Hyperplasia in Adult Goto-Kakizaki (GK/MolTac) Diabetic Rats.
abstract: Reduced beta cell mass in pancreatic islets (PI) of Goto-Kakizaki (GK) rats is frequently observed in this diabetic model, but knowledge on delta cells is scarce. Aiming to compare delta cell physiology/pathology of GK to Wistar rats, we found that delta cell number increased over time as did somatostatin mRNA and delta cells distribution in PI is different in GK rats. Subtle changes in 6-week-old GK rats were found. With maturation and aging of GK rats, disturbed cytoarchitecture occurred with irregular beta cells accompanied by delta cell hyperplasia and loss of pancreatic polypeptide (PPY) positivity. Unlike the constant glucose-stimulation index for insulin PI release in Wistar rats, this index declined with GK age, whereas for somatostatin it increased with age. A decrease of GK rat PPY serum levels was found. GK rat body weight decreased with increasing hyperglycemia. Somatostatin analog octreotide completely blocked insulin secretion, impaired proliferation at low autocrine insulin, and decreased PPY secretion and mitochondrial DNA in INS-1E cells. In conclusion, in GK rats PI, significant local delta cell hyperplasia and suspected paracrine effect of somatostatin diminish beta cell viability and contribute to the deterioration of beta cell mass. Altered PPY-secreting cells distribution amends another component of GK PI's pathophysiology.
authors.affiliation: Department No. 75, Institute of Physiology, Academy of Sciences, 14220 Prague, Czech Republic.
authors.forename: Lukáš
authors.initials: L
authors.lastname: Alán
authors.affiliation: Department No. 75, Institute of Physiology, Academy of Sciences, 14220 Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Olejár
authors.affiliation: Institute of Clinical & Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Cahová
authors.affiliation: Department No. 75, Institute of Physiology, Academy of Sciences, 14220 Prague, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Zelenka
authors.affiliation: Institute of Clinical & Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Berková
authors.affiliation: Teaching Thomayer Hospital and Third Medical School, Charles University, 14059 Prague, Czech Republic.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Smětáková
authors.affiliation: Institute of Clinical & Experimental Medicine, 14021 Prague, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Saudek
authors.affiliation: Teaching Thomayer Hospital and Third Medical School, Charles University, 14059 Prague, Czech Republic.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Matěj
authors.affiliation: Department No. 75, Institute of Physiology, Academy of Sciences, 14220 Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Ježek
mesh_terms: D000375:Aging; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental; D006965:Hyperplasia; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007329:Insulin Antagonists / Q000494:pharmacology; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000494:pharmacology; D010191:Pancreatic Polypeptide / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013004:Somatostatin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019864:Somatostatin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D007328:Insulin; D007329:Insulin Antagonists; D012333:RNA, Messenger; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D015282:Octreotide