The effects of fasting and refeeding on insulin-like growth factor-I stimulated glucose transport

Abstract

Insulin-like growth factor-I (IGF-I) is a known stimulator of glucose transport. IGF binding protein 1 (IGFBP1) is a protein that regulates the actions of IGF-I by binding to IGF-I which alters it's ability to bind to the IGF-I receptor. Diet and exercise may influence this system. While IGFBP1 levels increase with fasting or prolonged exercise, feeding will reverse this elevation. The intent of this study was to determine if an in vivo manipulation of IGFBP1 affects in vitro glucose transport in the rat soleus. Sixteen male Spaque Dawley rats were fasted for 12 hours. Half of the animals were then allowed a two hour ad libitum refeeding period. Animals were anesthetized and had their soleus muscles removed. Muscles were then randomly assigned to one of four treatment groups. Treatments involved an incubation in either 4 or 8 mM glucose in either the presence or absence of IGF-I (75 ng x ml"'). Final incubation for all treatment groups included [3H]-3-O-methylglucose (437 µCi x mM-) for the measurement of glucose transport. Following incubation, muscles were weighed, homogenized in 1 ml of 10% trichloroacetic acid, and centrifuged to precipitate out protein. 100 µl of the supernatant was added to 3 ml of scintillation fluid and analyzed in a scintillation counter. Glucose transport was determined by 3H activity. A statistical analysis of the various groups shows that there is no significant difference between fasted and refed animal for any specific treatment. However, when all the fasted and refed animals area grouped, glucose transport rate is significantly greater (p<0.05) in fasted (3.59 ± 0.44 µM x ml"' x hr) animals than in refed animals (2.56 ± 0.27 µM x ml"' x hr'). Additionally, muscles that were treated with IGF-I in 8 mM glucose demonstrated a greater rate of glucose transport (5.12 ± 0.68 µM x ml-1 x hr') than all other treatments (2.13 ± 0.39 to 2.90 ± .33 µM x ml-' x hr'). This study showed that IGF-I is a stimulator of glucose transport in an 8 mM glucose media. Additionally, the results show that glucose transport is greater if the animals are fasted. The differences between fasted and refed animals demonstrated in this study supports the hypothesis that diet manipulated IGFBP1 levels are able to alter the biological effects of IGF-I.