The GK Rat: A Prototype for the Study of Non-overweight Type 2 Diabetes

Abstract

Type 2 diabetes mellitus (T2D) arises when the endocrine pancreas fails to secrete sufficient insulin to cope with the metabolic demand because of β-cell secretory dysfunction and/or decreased β-cell mass. Defining the nature of the pancreatic islet defects present in T2D has been difficult, in part because human islets are inaccessible for direct study. This review is aimed to illustrate to what extent the Goto Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved to be a valuable tool offering sufficient commonalities to study this aspect. A comprehensive compendium of the multiple functional GK abnormalities so far identified is proposed in this perspective, together with their time-course and interactions. A special focus is given toward the pathogenesis of defective β-cell number and function in the GK model. It is proposed that the development of T2D in the GK model results from the complex interaction of multiple events: (1) several susceptibility loci containing genes responsible for some diabetic traits; (2) gestational metabolic impairment inducing an epigenetic programming of the offspring pancreas and the major insulin target tissues; and (3) environmentally induced loss of β-cell differentiation due to chronic exposure to hyperglycemia/hyperlipidemia, inflammation, and oxidative stress.

Comparison of GLUT1, GLUT2, GLUT4 and SGLT1 mRNA Expression in the Salivary Glands and Six Other Organs of Control, Streptozotocin-Induced and Goto-Kakizaki Diabetic Rats

“…Diabetic STZ rats were obtained as described elsewhere [8], GK rats were obtained from the Paris colony, initiated by the end of the 1980s [9] from the original Japanese colony [10] and maintained from that time at the University Paris-Diderot animal core [11]. Parotid and submaxillary glands, heart, kidney, liver, lung, soleus muscle and pancreas were removed and processed for quantitative real-time PCR analysis as previously described, according to the delta Ct method, the gene expression level of each mRNA being normalized to relative GAPDH (glyceraldehyde 3-phosphate dehydrogenase enzyme) mRNA [7].…”

HSF1 acetylation decreases its transcriptional activity and enhances glucolipotoxicity-induced apoptosis in rat and human beta cells

“…We thus used islets isolated from 10-week-old diabetic GK rats, one of the best characterised animal models of spontaneous type 2 diabetes [23] and islets from control Wistar rats to measure the expression of Hsf1 and some of its proposed transcriptional targets, namely Hspa1a, Dnajb1, Usp24 and Hhex [24,25] (Fig. 5a).…”

Abnormalities in the Metabolism of Fatty Acids and Triacylglycerols in the Liver of the Goto‐Kakizaki Rat: A Model for Non‐Obese Type 2 Diabetes

“…Unlike most animal models developed for T2D, the Goto-Kakizaki (GK) rat is an animal model of spontaneous-onset T2D without obesity. The GK rat exhibits mild hyperglycemia, impaired glucose tolerance, impaired insulin secretion, progressive reductions in the β-cell mass, and the development of long-term diabetic complications without obesity [6,7]. Impaired insulin sensitivity has also been reported not only in the skeletal muscles and adipose tissues of GK rats but also in their livers [8,9].…”