Regenerating 1 and 3b gene expression in the pancreas of type 2 diabetic Goto-Kakizaki (GK) rats.

Regenerating (REG) proteins are associated with islet development, β-cell damage, diabetes and pancreatitis. Particularly, REG-1 and REG-3-beta are involved in cell growth/survival and/or inflammation and the Reg1 promoter contains interleukin-6 (IL-6)-responsive elements. We showed by transcriptome analysis that islets of Goto-Kakizaki (GK) rats, a model of spontaneous type 2 diabetes, overexpress Reg1, 3α, 3β and 3γ, vs Wistar islets.

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.

Background/aims: The expression and localization of several distinct glucose transporters (GLUT1, GLUT2, GLUT4, and SGLT1) was recently characterized in the parotid gland of normal rats by quantitative real-time PCR analysis, immunohistochemistry and Western blotting. The major aims of the present study was to compare the mRNA expression of these glucose transporters in both the parotid gland and submaxillary gland of control rats, streptozotocin-induced diabetic rats and hereditarily diabetic Goto-Kakizaki rats.

Methods: Quantitative real-time PCR analysis was performed in the parotid and submaxillary salivary glands and, for purpose of comparison, also in the heart, kidney, liver, lung, muscle and pancreas from control animals and either streptozotocin-treated or Goto-Kakizaki rats.

The GK rat: a prototype for the study of non-overweight type 2 diabetes.

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.

cAMP-secretion coupling is impaired in diabetic GK/Par rat β-cells: a defect counteracted by GLP-1.

cAMP-raising agents with glucagon-like peptide-1 (GLP-1) as the first in class, exhibit multiple actions that are beneficial for the treatment of type 2 diabetic (T2D) patients, including improvement of glucose-induced insulin secretion (GIIS). To gain additional insight into the role of cAMP in the disturbed stimulus-secretion coupling within the diabetic β-cell, we examined more thoroughly the relationship between changes in islet cAMP concentration and insulin release in the GK/Par rat model of T2D. Basal cAMP content in GK/Par islets was significantly higher, whereas their basal insulin release was not significantly different from that of Wistar (W) islets.

Fatty acid pattern of pancreatic islet lipids in Goto-Kakizaki rats.

Perturbations of fatty acid content and pattern were recently documented in epididymal and parametrial lipids, as well as plasma, liver, spleen, and brain phospholipids and triglycerides of Goto-Kakizaki rats (GK). This study extends such an investigation to pancreatic islets from both control and GK rats. Groups of 5,500-14,560 islets were obtained from either control or GK rats (n = 3 in each case) and examined for their lipid fatty acid content.

Islet structure and function in the GK rat.

Type 2 diabetes mellitus (T2D) arises when the endocrine pancreas fails to secrete sufficient insulin to cope with the metabolic demand because of beta-cell secretory dysfunction and/or decreased beta-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.

Hippocampal neurovascular and hypothalamic-pituitary-adrenal axis alterations in spontaneously type 2 diabetic GK rats.

Metabolic and vascular consequences of diabetes mellitus induce several CNS complications. The dentate gyrus of the hippocampus, a well-recognized target for diabetic alterations, is a neurogenic area associated with memory and learning processes. Here, we explored the hippocampal neurogenesis and its microenvironment (astrocytes, vascularisation and glucocorticoid influence) in a spontaneous model of type 2 diabetes, the Goto-Kakizaki rat.

Islet endothelial activation and oxidative stress gene expression is reduced by IL-1Ra treatment in the type 2 diabetic GK rat.

Background: Inflammation followed by fibrosis is a component of islet dysfunction in both rodent and human type 2 diabetes. Because islet inflammation may originate from endothelial cells, we assessed the expression of selected genes involved in endothelial cell activation in islets from a spontaneous model of type 2 diabetes, the Goto-Kakizaki (GK) rat. We also examined islet endotheliuml/oxidative stress (OS)/inflammation-related gene expression, islet vascularization and fibrosis after treatment with the interleukin-1 (IL-1) receptor antagonist (IL-1Ra).

Adenine nucleotide pattern in rat pancreatic islets exposed to nutrient secretagogues.

The effects of D-glucose, D-mannose, D-galactose, Dglyceraldehyde, pyruvate, L-lactate, 2-ketoisocaproate, L-leucine, and/or L-glutamine on the ATP and ADP content of rat isolated pancreatic islets were reevaluated in order to compare changes evoked by these nutrient secretagogues in the islet ATP content and ATP/ADP ratio to their effects upon insulin release. Although being compatible with the fuel concept for nutrient-stimulated insulin secretion, the results of this study also argue against the monolithic view that the adenine nucleotide pattern in islet cells represents the sole coupling factor between metabolic and more distal events in the process of nutrient-stimulated insulin release.

Opposite effects of D-fructose on total versus cytosolic ATP/ADP ratio in pancreatic islet cells.

D-fructose (10 mM) augments, in rat pancreatic islets, insulin release evoked by 10 mM D-glucose. Even in the absence of D-glucose, D-fructose (100 mM) displays a positive insulinotropic action. It was now examined whether the insulinotropic action of D-fructose could be attributed to an increase in the ATP content of islet cells.

Fructokinase activity in rat liver, ileum, parotid gland, pancreas, pancreatic islet, B and non-B islet cell homogenates.

The presence of fructokinase (ketohexokinase) in rat pancreatic islet homogenates was previously documented. However, no information was so far available on the activity of this enzyme in islets relative to that in other tissues and on the respective contribution of insulin-producing B cells and non-B islet cells. The present study provides such an information.

Restitution of defective glucose-stimulated insulin secretion in diabetic GK rat by acetylcholine uncovers paradoxical stimulatory effect of beta-cell muscarinic receptor activation on cAMP production.

Because acetylcholine (ACh) is a recognized potentiator of glucose-stimulated insulin release in the normal beta-cell, we have studied ACh's effect on islets of the Goto-Kakizaki (GK) rat, a spontaneous model of type 2 diabetes. We first verified that ACh was able to restore the insulin secretory glucose competence of the GK beta-cell. Then, we demonstrated that in GK islets 1) ACh elicited a first-phase insulin release at low glucose, whereas it had no effect in Wistar; 2) total phospholipase C activity, ACh-induced inositol phosphate production, and intracellular free calcium concentration ([Ca2+]i) elevation were normal; 3) ACh triggered insulin release, even in the presence of thapsigargin, which induced a reduction of the ACh-induced [Ca2+]i response (suggesting that ACh produces amplification signals that augment the efficacy of elevated [Ca2+]i on GK exocytosis); 4) inhibition of protein kinase C did not affect [Ca2+]i nor the insulin release responses to ACh; and 5) inhibition of cAMP-dependent protein kinases (PKAs), adenylyl cyclases, or cAMP generation, while not affecting the [Ca2+]i response, significantly lowered the insulinotropic response to ACh (at low and high glucose).

Comparison between D-[3-3H]- and D-[5-3H]glucose and fructose utilization in pancreatic islets from control and hereditarily diabetic rats.

The metabolism of D-glucose and/or D-fructose was investigated in pancreatic islets from control rats and hereditarily diabetic GK rats. In the case of both D-glucose and D-fructose metabolism, a preferential alteration of oxidative events was observed in islets from GK rats. The generation of 3HOH from D-[5-3H]glucose (or D-[5-3H]fructose) exceeded that from D-[3-3H]glucose (or D-[3-3H]fructose) in both control and GK rats.

Metabolism of D-[3-3H]glucose, D-[5-3H]glucose, D-[U-14C]glucose, D-[1-14C]glucose and D-[6-14C]glucose in pancreatic islets in an animal model of type-2 diabetes.

This study aims at exploring specific aspects of D-glucose metabolism, so far not yet investigated, in pancreatic islets from adult control rats and animals (STZ rats) injected with streptozotocin during the neonatal period. The latter animals, which represent a current model of type-2 diabetes, displayed a lower body weight, higher plasma D-glucose concentration and lower insulinogenic index than control rats. The protein, DNA and insulin content were all also lower in islets prepared from STZ, rather than control rats.