HAIGWOOD, J.T.; PEREZ, M.*; KELLEY, K.M.: Effects of Glucagon and Glucagon-Like Peptide-1 (GLP-1) on Glycemic Status and Glucose Production in the Isletectomized Diabetic Goby

In the teleost fish, Gillichthys mirabilis, a total endocrine pancreatic isletectomy procedure induces hyperglycemia and a host of other symptoms typical of insulin-dependent diabetes mellitus (IDDM). Thus, in the isletectomized (Ix) goby, hepatic delivery of all pancreatic hormones is ceased. In contrast to IDDM in the streptozotocin-treated rat, in which only insulin is absent and diabetic hyperglycemia occurs within 12 hr, the Ix goby does not express significant hyperglycemia until after 10-15 d, suggestive of a lack of hyperglycemic action of a pancreatic factor(s) during this period. Treatment of 7-d Ix gobies (not yet symptomatic) with porcine or human glucagon at 1-5 �g/g body weight induces a significant hyperglycemia comparable to that in fully diabetic rats or gobies (20 d post-Ix). Similarly, treatment with identical doses of human or coho salmon GLP-1 induces a similar hyperglycemic response in the 7-d Ix goby. When liver explants from the glucagon- or GLP-1-treated Ix gobies were tested in vitro, they were determined to release glucose at a 2-fold greater rate per mg tissue (p<0.05) than liver explants from untreated Ix gobies. These data suggest that glucagon and GLP-1 are diabetogenic factors in the Ix goby capable of enhancing hepatic glucose output. [Support by NSF grants IBN 9600783, DUE 9651189, & NIH grant GM50089]