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.
Highlights
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder comprising both peripheral insulin resistance [1,2,3,4] and/or pancreatic beta cell dysfunction [2,3,4,5]
Besides insulin secretion the SST secretion as a response to glucose was found impaired in the perfused pancreas of GK rats [23]; we focused on delta cells and SST pancreatic islets (PI) content in fully developed diabetes
intravenous glucose tolerance test (IVGTT): rats were injected with 20% glucose into tail vein (1 g per kg body weight) and blood glucose was measured at the 10 min time intervals up to 60 min
Summary
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder comprising both peripheral insulin resistance [1,2,3,4] and/or pancreatic beta cell dysfunction [2,3,4,5]. The impaired insulin responsiveness of peripheral tissues places increasing demands on insulin secretion. This may eventually lead to failure of beta cells. Genetic predisposition 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. An insufficiency for compensatory overproduction of beta cells in pancreatic islets (PI) due to beta cell dysfunction and/or loss of beta cell mass [3] may contribute
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