title: Insulin action in previously diabetic rats receiving graded numbers of islets of Langerhans.
abstract: We characterized insulin sensitivity in islet transplanted rats receiving from 500 to 3000 islets. Male Wistar Furth rats made previously diabetic with streptozotocin (55 mg/kg) were infused intraportally with islets of Langerhans (500 islets: n = 8; 1000: n = 6; 2000: n = 6; 3000: n = 5) from syngeneic donors and compared with sham-operated controls (n = 7). At four weeks after islet transplantation, fasting blood glucose was not significantly different between groups (500: 5.1 +/- 0.3; 1000: 4.8 +/- 0.3; 2000: 5.1 +/- 0.3; 3000: 4.6 +/- 0.1; control: 4.7 +/- 0.2 mM; P = 0.6146), and fasting plasma insulin was also not different (P = 0.28). The acute insulin response to glucose (0.3 g/kg i.v.) was correlated with islet equivalent mass (r = 0.63, P = 0.004; transplant rats only); islet transplant animals presented a range of acute insulin secretion from 3 to 90% of control values. Insulin action was measured in vivo in fasted, conscious animals during a hyperinsulinemic-euglycemic glucose clamp with insulin infused at 29 and 72 nmol/kg/min. Despite a wide range of islet mass and insulin secretory capacity, there was no significant difference in the glucose infusion rate between islet groups at either insulin level (P = 0.8211, P = 0.8021). There was also no difference in the glucose infusion rate normalized to the prevailing insulin level (P = 0.1638, P = 0.2302). Thus, our results demonstrate that the islet transplanted rat is consistent with other animal studies and human studies illustrating that a diminished insulin secretion does not necessarily precipitate insulin resistance.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: B W
authors.initials: BW
authors.lastname: Tobin
authors.forename: J T
authors.initials: JT
authors.lastname: Lewis
authors.forename: B L
authors.initials: BL
authors.lastname: Tobin
authors.forename: D T
authors.initials: DT
authors.lastname: Finegood
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005215:Fasting; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose