Effect of Insulin-Like Growth factor -1 treatment on glucose metabolism in a transgenic mouse models of type-2 Diabetes Mellitus

PENNISI P; GAVRILOVA, O; SETSER-PORTAS, J; JOU, W; CLEMMONS, D; LEROITH, D

Bethesda, MD

Jornada; . 5th Annual Hipanic Scientific Day, National Institutes of Health.; 2004

NIH

Administration of rh1GF-1 has been shown to improve glucose control and liver and muscle insulin sensitivity in patients with type-2 DM. The effect of rh1GF-1 treatment was evaluated in a mouse model of type-2 DM (MKR) which expresses a dominant negative (DN) form of the human IGF-IR under the control of the muscle creatine kinase promoter specifically in muscle. MKR mice have impaired IGF-1 and insulin signaling in skeletal muscle leading to severe insulin resistance in liver and fat and eventually type 2 DM. Six week old MKR male mice were treated with either saline (n=7) or rh1GF-1 (n=7) (1 mg/Kg) twice daily (IP) for 2 weeks. Body weight, body composition, muscle and organ weight were measured at the end of the treatment. After 2 weeks of IGF-1 treatment body weight was increased in IGF-1 treated compared to saline treated mice [23.00 ± 0.67 vs 20.60± 0.43 p<0.005]. Body composition showed increased lean mass [18.38 ± 0.61g vs 15.98± 0.39g; 79.7± 0.6 vs 77.6 ±0.6 %, p< 0.03] and a tendency to reduce fat mass [1.61 ± 0.18g vs 1.89± 0.13g; 6.98± 0.79 vs 9.21 ± 0.68 %, p=0.059]. Basal glucose levels in the fed state decreased significantly [337.7 ± 17.9 vs 208.9 ± 34 mg/dl, p< 0.025] at the end of the treatment. Hyperinsulinemia-euglycemia calmp studies are being performed to determine the site of improved insulin sensitivity in the face of insulin resistance at the level of the muscle in the MKR mice. Sunday, June 5, 2005 11 :00 AM POSTER SESSION: BASIC - Diabetes I (11 :00 AM-12:00 PM and 2:30 PM-3:30 PM) 0.025] at the end of the treatment. Hyperinsulinemia-euglycemia calmp studies are being performed to determine the site of improved insulin sensitivity in the face of insulin resistance at the level of the muscle in the MKR mice. Sunday, June 5, 2005 11 :00 AM POSTER SESSION: BASIC - Diabetes I (11 :00 AM-12:00 PM and 2:30 PM-3:30 PM) of the treatment. After 2 weeks of IGF-1 treatment body weight was increased in IGF-1 treated compared to saline treated mice [23.00 ± 0.67 vs 20.60± 0.43 p<0.005]. Body composition showed increased lean mass [18.38 ± 0.61g vs 15.98± 0.39g; 79.7± 0.6 vs 77.6 ±0.6 %, p< 0.03] and a tendency to reduce fat mass [1.61 ± 0.18g vs 1.89± 0.13g; 6.98± 0.79 vs 9.21 ± 0.68 %, p=0.059]. Basal glucose levels in the fed state decreased significantly [337.7 ± 17.9 vs 208.9 ± 34 mg/dl, p< 0.025] at the end of the treatment. Hyperinsulinemia-euglycemia calmp studies are being performed to determine the site of improved insulin sensitivity in the face of insulin resistance at the level of the muscle in the MKR mice. Sunday, June 5, 2005 11 :00 AM POSTER SESSION: BASIC - Diabetes I (11 :00 AM-12:00 PM and 2:30 PM-3:30 PM) 0.025] at the end of the treatment. Hyperinsulinemia-euglycemia calmp studies are being performed to determine the site of improved insulin sensitivity in the face of insulin resistance at the level of the muscle in the MKR mice. Sunday, June 5, 2005 11 :00 AM POSTER SESSION: BASIC - Diabetes I (11 :00 AM-12:00 PM and 2:30 PM-3:30 PM) twice daily (IP) for 2 weeks. Body weight, body composition, muscle and organ weight were measured at the end of the treatment. After 2 weeks of IGF-1 treatment body weight was increased in IGF-1 treated compared to saline treated mice [23.00 ± 0.67 vs 20.60± 0.43 p<0.005]. Body composition showed increased lean mass [18.38 ± 0.61g vs 15.98± 0.39g; 79.7± 0.6 vs 77.6 ±0.6 %, p< 0.03] and a tendency to reduce fat mass [1.61 ± 0.18g vs 1.89± 0.13g; 6.98± 0.79 vs 9.21 ± 0.68 %, p=0.059]. Basal glucose levels in the fed state decreased significantly [337.7 ± 17.9 vs 208.9 ± 34 mg/dl, p< 0.025] at the end of the treatment. Hyperinsulinemia-euglycemia calmp studies are being performed to determine the site of improved insulin sensitivity in the face of insulin resistance at the level of the muscle in the MKR mice. Sunday, June 5, 2005 11 :00 AM POSTER SESSION: BASIC - Diabetes I (11 :00 AM-12:00 PM and 2:30 PM-3:30 PM) 0.025] at the end of the treatment. Hyperinsulinemia-euglycemia calmp studies are being performed to determine the site of improved insulin sensitivity in the face of insulin resistance at the level of the muscle in the MKR mice. Sunday, June 5, 2005 11 :00 AM POSTER SESSION: BASIC - Diabetes I (11 :00 AM-12:00 PM and 2:30 PM-3:30 PM) mg/dl, p< 0.025] at the end of the treatment. Hyperinsulinemia-euglycemia calmp studies are being performed to determine the site of improved insulin sensitivity in the face of insulin resistance at the level of the muscle in the MKR mice. Sunday, June 5, 2005 11 :00 AM POSTER SESSION: BASIC - Diabetes I (11 :00 AM-12:00 PM and 2:30 PM-3:30 PM)