Fuel-induced insulin release in vitro from insulinomas transplanted into the rat kidney.
We studied the release of insulin, glucagon, and somatostatin in response to glucose, glyceraldehyde (GA), and alpha-ketoisocaproate (KIC) from rat kidneys containing transplanted insulinomas. Kidneys were perfused about 11 wk after transplantation when the plasma glucose concentration of the fed animals had decreased from 180 +/- 7 to 95.1 +/- 9.9 mg/dl and plasma insulin concentrations had increased from 2.6 +/- 0.5 to 14.2 +/- 2.0 ng/ml. The insulin content of the tumor-containing kidney ranged from 40 to 679 micrograms; the glucagon and somatostatin concentrations ranged from undetectable levels to 3.7 micrograms and 248 ng, respectively. The average response to 30 mM glucose and 10 mM GA was a four- to fivefold increase in insulin secretion, whereas 30 mM KIC caused a 16- to 28-fold increase. In vitro stimulation of the insulinoma with 30 mM glucose primed the beta-cell response to a second stimulus following a short rest period. Cytochalasin B did not enhance this primed glucose response. Diazoxide inhibited glucose, GA, and KIC-stimulated insulin release. Glucose, GA, and KIC stimulated glucagon release in 2 of 17 insulinomas studied here. Somatostatin release was not seen in any of the experiments. These findings show that this islet cell tumor transplanted under the kidney capsule releases insulin in response to physiologic and model fuel substances. Thus, this particular transplantable tumor offers an opportunity to study the biochemistry and biophysics that underlie fuel-stimulated insulin release.
D007516:Adenoma, Islet Cell / Q000378:metabolism*; D000818:Animals; D003571:Cytochalasin B / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D005985:Glyceraldehyde / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D007651:Keto Acids / Q000494:pharmacology*; D007668:Kidney / Q000502:physiology*; D008297:Male; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D013004:Somatostatin / Q000378:metabolism
D007328:Insulin; D007651:Keto Acids; D005985:Glyceraldehyde; D003571:Cytochalasin B; D013004:Somatostatin; C013082:alpha-ketoisocaproic acid; D005934:Glucagon; D005947:Glucose; D003981:Diazoxide