Research Article Delta Cell Hyperplasia in Adult Goto-Kakizaki (GK/MolTac) Diabetic Rats Lukáš Alán, 1 Tomáš Olejár, 1 Monika Cahová, 2 Jaroslav Zelenka, 1 Zuzana Berková, 2 Magdalena Smjtáková, 3 František Saudek, 2 Radoslav Matjj, 3 and Petr JeDek 1 1 Department No. 75, Institute of Physiology, Academy of Sciences, 14220 Prague, Czech Republic 2 Institute of Clinical & Experimental Medicine, 14021 Prague, Czech Republic 3 Teaching omayer Hospital and ird Medical School, Charles University, 14059 Prague, Czech Republic Correspondence should be addressed to Petr Jeˇ zek; jezek@biomed.cas.cz Received 28 April 2015; Revised 22 May 2015; Accepted 31 May 2015 Academic Editor: Chen Chen Copyright © 2015 Luk´ aˇ s Al´ an et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 diferent 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, signifcant local delta cell hyperplasia and suspected paracrine efect 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. 1. Introduction Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder comprising both peripheral insulin resistance [1–4] and/or pancreatic beta cell dysfunction [2–5]. Te impaired insulin responsiveness of peripheral tissues places increasing demands on insulin secretion. Tis may eventually lead to failure of beta cells. During the preclinical phase, pancreatic beta cells are still able to overcome the escalating insulin resistance, which may last for many years. Genetic predispo- sition and ongoing metabolic stress, lipid accumulation in the pancreas, glucagon overproduction, and beta cell structural damage and death as well as impairment of normal beta cell biogenesis lead to a gradual decline of the overall islet function. Also, an insufciency for compensatory overpro- duction of beta cells in pancreatic islets (PI) due to beta cell dysfunction and/or loss of beta cell mass [3] may contribute. Besides beta cells, PI are composed of alpha, delta, epsilon, and PP cells secreting glucagon, somatostatin (SST), ghrelin, and pancreatic polypeptide (PPY), respectively [4]. SST inhibits the release of insulin and glucagon in a paracrine manner [6]. All known beta cell secretagogues, such as glu- cose, arginine, gastrointestinal hormones, and tolbutamide, support the release of SST from delta cells [7]. PPY plasma levels increase with age as well as in both diabetes types [8]. But in type 2 diabetic patients, diet-induced weight loss and improvement of beta cell function are accompanied by a decrease in PPY plasma levels [9]. Recently, beta cell dediferentiation into alpha cells has been suggested to participate in human type 2 diabetes etiology [10, 11]. A diferentiation shif can arise when certain transcription fac- tors diminish, like Nkx6.1, which controls a gene regulatory network required for establishing and maintaining beta cell identity [12, 13]. Also, the homeodomain transcription factor Hindawi Publishing Corporation Journal of Diabetes Research Volume 2015, Article ID 385395, 16 pages http://dx.doi.org/10.1155/2015/385395