Cells grown in culture from rat islet cell tumor (parent cells) and clones obtained from them were used in this study. Parent cells secreted primarily insulin and somatostatin with very small quantities of glucagon. The clones, based on hormone content and secretion, were divided into three phenotypic groups: insulin secreting, somatostatin secreting, and nonsecreting clones. Specific receptors for insulin, glucagon, and somatostatin were demonstrated on parent cells and clones. Parent cells bound 4.12 +/- 0.46% insulin, 2.11 +/- 0.29% glucagon, and 2.49 +/- 1.24% somatostatin per 2 x 10(6) cells. Characteristic hormone binding patterns were observed in insulin secreting versus somatostatin secreting clones. Insulin secreting versus somatostatin secreting clones. Insulin secreting clones bound less insulin than somatostatin and other noninsulin-secreting clones (P less than 0.02). In contrast, somatostatin secreting clones bound more somatostatin than non-somatostatin-secreting clones (P less than 0.05). Somatostatin-secreting clones had a significantly greater number of receptors for all three hormones. The difficulties involved in the interpretation of the quantitative aspects of binding in the presence of continued hormone secretion are discussed. Nonetheless, the presence of receptors on the cells for hormones secreted by the same cells strongly suggests autoregulation. The apparent low affinity of some of these receptors and the presence of receptors for all three islet cell hormones on all islet cells supports the likelihood of paracrine controls.

No abstract

The SHR/N-cp rat is a new genetically obese model for non-insulin-dependent diabetes mellitus. Expression of the diabetes is enhanced by a high-sucrose (54%) diet. After 4 wk on the diet, the cp/cp rats weigh significantly more than their +/? controls, have postprandial hyperglycemia (greater than 400 mg/dl), and are hyperinsulinemic, with immunoreactive insulin (IRI) levels 10- to 20-fold greater than controls. Total pancreatic IRI tends to be increased 1.6-fold in the cp/cp rats (although not significantly). There is no increase in pancreatic proinsulin content as a percent of total IRI. Studies of in vitro pancreatic function were carried out with the isolated nonrecirculating perfused pancreas method. The cp/cp rats (n = 10) showed impaired or absent IRI responses to 16.5 mM glucose, whereas +/? rats (n = 9) responded with classic biphasic curves. Comparison of insulin secreted in 20 min revealed a greater than 53% decrease in IRI secretion in cp/cp rats (P less than .05). A paradoxical hypersecretion of IRI at glucose concentrations of 0-2.7 mM was noted in cp/cp but not lean rats, i.e., 1.8 +/- 0.2 mU/min IRI in cp/cp rats vs. 0.04 +/- 0.007 mU/min in +/? rats. Perfusion of pancreases for 45 min with buffers containing no glucose resulted in restoration of a normal biphasic IRI response to 16.5 mM glucose in the cp/cp rats, whereas response in the lean rats was markedly reduced. Brisk IRI responses to 10 mM arginine in buffers with no glucose also occurred in cp/cp but not +/? rats. Glucagon secretion was relatively suppressed in the cp/cp rats.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

The effect of 48 h of fasting in C57B1/6J-ob/ob and +/+ mice on body weight (BW), blood glucose (BG), serum immunreactive insulin (IRI), plasma immunoreactive glucagon (IRG) and on tissue levels of cyclic adenosine monophosphate (cAMP) were studied. Both groups of mice lost weight and demonstrated a decrease in BG and IRI with fasting. However, the BG and IRI of the ob/ob animals were initially highter and remained higher than those of the 2% of their initial weight while the +/+ lost 14 %. The +/+ mice exhibited an increase in cAMP levels in skeletal muscle, fat and liver with fasting, while the ob/ob mice had increased levels of cAMP in fat, but not in muscle. They also had a paradoxical decrease in liver cAMP levels with fasting, and associated with this was the lack of stimulation of glycogenolysis. Glycogenolysis was significant in the livers of fasted +/+ mice. The plasma IRG levels of the fed ob/ob mice were significantly higher (1.8) times) than those of the fed +/+ mice. Islet cAMP levels were decreased with fasting in ob/ob mice. However, the levels were significantly higher in 48-h faster ob/ob mice compared to the fasted +/+ group. The apparent paradoxical response to fasting observed in the livers of the ob/ob mice remains unexplained.