Polyamines in pancreatic islets of obese-hyperglycemic (ob/ob) mice of different ages

Abstract

To further evaluate the role of polyamines in insulin production and cell replication in diabetic pancreatic islets, we have studied hyperplastic islets of obese-hyperglycemic mice of different ages and normal islets of the same strain. The aims of the study were to investigate the impact of the diabetic state and aging on polyamine contents and requirements in these islets. Cultured islets from lean and obese animals contained significantly less polyamines than freshly isolated islets. Spermine-to-spermidine ratio was elevated in freshly isolated islets from young obese mice compared with those from lean mice. In islets from old obese animals, spermidine content was decreased, whereas the content of spermine was not different from that of young obese mice. The physiological significance of polyamines was investigated by exposing islets in tissue culture to inhibitors of polyamine synthesis. This treatment caused a partial polyamine depletion in whole islets but failed to affect polyamine content of cell nuclei. Insulin content was not affected in polyamine-deficient islets of obese mice, irrespective of age, in contrast to decreased islet insulin content in polyamine-depleted young lean animals. Polyamine depletion depressed DNA synthesis rate in obese mouse islets; in lean mice it actually stimulated DNA synthesis. We concluded that important qualitative and quantitative differences exist between islets from obese-hyperglycemic and normal mice with respect to polyamine content and requirements of polyamines for regulation of insulin content and cell proliferation. The results suggest that spermine may be involved in mediating the rapid islet cell proliferation noted early in obese-hyperglycemic syndrome, but changes in spermine concentration do not seem to account for the decline in islet cell DNA synthesis in aged normoglycemic animals.

Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases

“…In fact, emerging evidence suggests that increased levels of polyamines in white adipose tissue, liver or skeletal muscle could stimulates energy expenditure and confer resistance to diet-induced obesity and non-alcoholic fatty liver disease (147, 148). In addition, a number of studies using different obesity animal models have reported altered levels of polyamines in adipose tissue (150), liver (151, 152), pancreatic islets (153), and urine (154). In addition, blood polyamines have been shown to be significantly higher in obese children compared to non-obese controls (155).…”

Role of caspases in the regulation of apoptotic pancreatic islet beta‐cells death

“…This effect was blocked by a Ca 2þ chelator, BAPTA-AM, and by an inhibitor of a Ca 2þ -dependent protease, calpain. These demonstrated that excessive NO production induces apoptosis, wherein an increase in [Ca 2þ ]i and resultant activation of calpain play a key role (Sjoholm et al, 2001). Whereas, alterations in cytosolic Ca 2þ homoeostasis do have a significant role in certain forms of beta-cell death, Bai et al demonstrated they do not contribute to the pathway of apoptosis evoked by hA in islet beta-cells (Nakata et al, 1999).…”

Type 2 Diabetes Is Associated with a Different Pattern of Serum Polyamines: A Case–Control Study from the PREDIMED-Plus Trial

“…In transgenic mouse models, the dysregulation of polyamine metabolism has been shown to impact glucose, lipid and energy homeostasis [9,10,11,12,13,14]. In addition, a number of studies using animal models of obesity have reported impaired levels of polyamines in adipose tissue [15], liver [16,17], pancreatic islets [18], and urine [19].…”

“…In the pancreas, polyamines are mainly located within the secretory granules of the islet β cells [30], where they have been implicated in proinsulin biosynthesis and insulin secretion [31]. Islet polyamine levels diminish with both age and obesity [18], suggesting that alterations in the intracellular levels of polyamines might affect β cell function. Remarkably, transgenic mice which overexpress the polyamine catabolic enzyme spermidine/spermine acetyltransferase (SSAT), which contains higher levels of putrescine and reduced levels of spermidine and spermine in the pancreatic islets, display impaired glucose-stimulated insulin secretion [11].…”