Exercise improves glucose homeostasis that has been impaired by a high-fat diet by potentiating pancreatic β-cell function and mass through IRS2 in diabetic rats

Abstract

In this study, we investigated the effects of a high-fat diet and exercise on pancreatic beta-cell function and mass and its molecular mechanism in 90% pancreatectomized male rats. The pancreatectomized diabetic rats were given control diets (20% energy) or a high-fat (HF) diet (45% energy) for 12 wk. Half of each group was given regular exercise on an uphill treadmill at 20 m/min for 30 min 5 days/wk. HF diet lowered first-phase insulin secretion with glucose loading, whereas exercise training reversed this decrease. However, second-phase insulin secretion did not differ among the groups. Exercise increased pancreatic beta-cell mass. This resulted from stimulated beta-cell proliferation and reduced apoptosis, which is associated with potentiated insulin or IGF-I signaling through insulin receptor substrate-2 (IRS2) induction. Although the HF diet resulted in decreased proliferation and accelerated apoptosis by weakened insulin and IGF-I signaling from reduction of IRS2 protein, beta-cell mass was maintained in HF rats just as much as in control rats via increased individual beta-cell size and neogenesis from precursor cells. Consistent with the results of beta-cell proliferation, pancreas duodenal homeobox-1 expression increased in the islets of rats in the exercise groups, and it was reduced the most in rats fed the HF diet. In conclusion, exercise combined with a moderate fat diet is a good way to maximize beta-cell function and mass through IRS2 induction to alleviate the diabetic condition. This study suggests that dietary fat contents and exercise modulate beta-cell function and mass to overcome insulin resistance in two different pathways.

The time has come to test the beta cell preserving effects of exercise in patients with new onset type 1 diabetes

“…Choi and colleagues reported that training enhanced beta cell proliferation and mass in 90% Px rats [11]. This finding was supported by Park et al, who demonstrated that training prevented the decline in first-phase insulin secretion in perfused islets and increased beta cell mass (via increased proliferation and reduced apoptosis) from high-fatfed 90% Px rats [12]. The increase in insulin-positive cells measured by immunohistochemistry reported across these studies varied from 20 to 50%.…”

“…For example, GH increases beta cell proliferation in vitro [9] and protects beta cell lines against IL-1β-, IFN-γ-and TNF-α-induced apoptotic cell death [10]. Increased IGF-1 signalling is thought to play a role in the increase in beta cell mass seen with exercise in 90% pancreatectomised (Px) rats [11,12]. IL-6, which is increased during exercise and elicits the increased circulating levels of GLP-1 during exercise, has an indirect effects on beta cell proliferation via GLP-1 [13].…”

The Effect of Three Months of Resistance Training on TCF7L2 Expression in Pancreas Tissues of Type 2 Diabetic Rats

“…In fact, although an increase in insulin resistance results in an increased mass of beta cells to secrete more insulin to compensate for insulin resistance (22)(23)(24), severe long-lasting insulin resistance is associated with reduced proliferation of beta cells. As a result, in response to long-term insulin resistance, levels of beta cell mass are not maintained for adequate secretion of insulin (25). If the capacity of insulin secretion is sufficient to compensate for insulin resistance, people with insulin resistance will not develop diabetes (22).…”

“…In addition, a Korean study showed that a significant proportion of patients with type 2 diabetes are not obese and their insulin levels are normal or below normal (30). These studies point out in general that the non-obese Asians secrete insufficient amounts of insulin during insulin resistance, leading ultimately to type 2 diabetes (25,28). In recent years, researchers have found 70 genetic variants with the risk for diabetes, but TCF7L2 is still identified as the most im-portant diabetes susceptibility gene, so that the gene has carriers and variants with the greatest risk of type 2 diabetes (21,29).…”

“…In this context, some studies have noted that both diet and physical activity increase insulin secretion, while functional mechanisms are independent of each other. Diet increases beta cell mass through hypertrophy to overcome insulin resistance, while exercise training increases beta cell mass through hyperplasia, which is displayed as increased beta cell proliferation and reduced apoptosis (25). In addition, some studies have reported that exercise reduces symptoms of hepatic insulin through reducing hepatic glucose release in hyperinsulinemic conditions (46,47).…”