Long-term physical training increases liver IGF-I in diabetic rats

Abstract

Diabetes reduces the serum levels of insulin-like growth factor-I (IGF-I) and physical training may prevent this reduction. Almost all circulating IGF-I is produced and secreted by the liver. To examine the influence of moderate physical training on liver IGF-1 levels in diabetes, male Wistar rats were given a single dose of alloxan (30 mg/kg b.w.) to induce diabetes and then randomly allocated to sedentary or trained groups. The training protocol consisted of a 1 h swimming session/day, five days/week for eight weeks with a load corresponding to 5% of the body weight. These two groups were compared with sedentary or trained non-diabetic rats (controls). A subcutaneous insulin tolerance test (ITT) was performed at the 6th week of experiment. At the end of the training period, the rats in all groups were sacrificed and blood was collected for the quantification of hematocrit and serum glucose, insulin, triglycerides, albumin, GH and IGF-1. Skeletal muscle and hepatic glycogen levels and hepatic triglyceride, protein, DNA and IGF-I concentrations were also determined. Diabetes reduced the serum insulin, GH and IGF-I concentrations, and the hepatic protein/DNA ratio and IGF-I concentrations, but increased serum glucose and triglyceride levels. Serum glucose removal during ITT was increased in the trained diabetic animals compared to sedentary control. Physical training reduced the serum glucose and triglyceride levels but increased the muscle glycogen content and restored the hepatic protein/DNA ratio and serum and hepatic IGF-I in diabetic rats. In conclusion, long-term chronic exercise improved the metabolic state and attenuated the reduction in serum and hepatic IGF-I concentrations caused by diabetes.

Introduction

Insulin-like growth factor-I (IGF-I) is a major endocrine, paracrine and autocrine regulator of growth and metabolism, with important actions in normal tissue growth and regeneration in animals and humans. Almost all circulating IGF-I is produced and secreted by the liver [1] and IGF-I concentrations are altered in several pathological states [2]. IGF-I is involved in wide range of biological phenomena, including metabolic disorders such as diabetes [2].

Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. The hyperglycemia in diabetes causes extensive damage and dysfunction in various organs, including the liver [3]. Diabetes impairs growth and may modify serum [4], [5] and IGF-I concentrations [6]. The precise mechanisms involved in the decrease in circulating and hepatic IGF-I levels is unclear, but may be related to a reduction in circulating GH levels or in the tissue responsiveness to GH [3], [5], [6], [7].

Type 1 diabetes is characterized by β-cell destruction and IGF-I is decreased in this condition [5], [8]. In rats, reversal of type 1 diabetes will require β-cell regeneration and prevention of recurring autoimmunity. Interessantly pancreatic expression of IGF-I may regenerate and protect β-cell mass in type 1 diabetes [9]. Evenmore, total insulin and IGF-I resistance in β-pancreatic cells causes overt diabetes [10], [11].

Physical training modulates glucose homeostasis in diabetics and prevents some damages by increasing the sensitivity and responsiveness to insulin [12], [13]. Several of the beneficial effects of exercise result from interactions between specific hormones and growth factors such as IGF-1 [14]. However, the relationship between physical training and IGF-I levels is uncertain since exercise has been reported to decrease, increase or not alter IGF-I concentrations [15]. The IGF-I response to physical training depends on the intensity of training: short-term physical training (three days to five weeks) reduces circulating IGF-I levels whereas prolonged training (>5–6 weeks) increases circulating IGF-I levels [16], [17]. We have previously shown that in normal and diabetic rats, short-term physical training (four weeks) decreases blood IGF-I concentrations, whereas six weeks of physical training does not change the blood IGF-I concentrations in control rats but restores this parameter in diabetic rats [5], [18]. Similarly, diabetes also reduces the muscle IGF-I concentrations but these are restored by chronic exercise [5].

The precise source of blood IGF-I in trained diabetic animals and humans remains uncertain [19], but probably involves the liver since there is a marked reduction (>80%) in the serum IGF-I concentrations of mice with IGF-I-deficient livers [1], [19], [20]. In the present study, we investigated the effects of long-term moderate physical training on the serum and hepatic IGF-I concentrations in diabetic rats.