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Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted nutrient-induced release of pancreatic polypeptide (PP). To investigate the possible role of PP on glucose metabolism, we studied male patients with documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic glucose production (HGP) and overall glucose disposal rates were determined by [3-3H]glucose infusion during a hyperinsulinemic-euglycemic clamp during three separate admissions. Basal rates of HGP were higher in CP patients. In response to an infusion of insulin (60 pmol.m-2.min-1), HGP fell 91 +/- 5% in NL subjects but only 68 +/- 8% in CP subjects (P < 0.05). One month later, the clamp was repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol.kg-1.min-1). HGP before the insulin infusion and its subsequent suppression (NL: 83 +/- 5%; CP: 86 +/- 15%) were nearly identical between groups. In follow-up studies 1 month after the PP infusion, HGP both basally and in response to insulin alone were similar to the first study. During oral glucose tolerance tests (OGTT) performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels (approximately -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month after the PP treatment showed a return to pretreatment responses. We conclude that chronic pancreatitis accompanied by PP deficiency is associated with partial hepatic resistance both in the basal state and in response to hyperinsulinemia. This impairment is reversed after iv PP administration. PP deficiency may therefore play a role in the development of pancreatogenic diabetes caused by pancreatic injury.

Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulinmediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1–34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3±0.2 versus 9.9±0.1 mg/dl, P

It has been hypothesized that opioid peptides play a role in the development of obesity. The opiate antagonist naltrexone decreases glucose-stimulated insulin release, while the sensitivity of diabetic rats to naloxone-induced satiety is increased. These findings suggest a possible interaction between glucose concentrations and opiate antagonists in the control of food intake. In three experiments the energy balance and glucose regulatory responses of Zucker obese and lean rats to chronic administration of nalmefene, an opiate antagonist, were measured. Nalmefene, when injected subcutaneously or added to feed for 21 days, decreased food intake and weight gain of obese and lean rats. These responses were more pronounced during the first week of treatment and were greater in obese than lean rats. Nalmefene increased glucose concentrations during day 1 and weeks 1, 2 and 3 only when given subcutaneously. Nalmefene given intragestrically attenuated glucose-stimulated increases in insulin release only in obese rats. Thus, chronic nalmefene administration is not likely to be an effective treatment for obesity or diabetes.

Rabbits and guinea-pigs were immunized with various pancreatic antigens in Freund's adjuvant. Rabbits received unfractionated bovine insulin and the "A" component and "single peak" insulin separated from it by gel-filtration. All produced antibodies capable of reacting with porcine insulin but none were found to have pancreatic lesions when killed up to 6 weeks after initial injection. Guinea-pigs immunized with bovine "A" component developed pancreatic peri-ductulitis which appeared most frequently (10/20) in animals killed 30 days after a single injection and less frequently in animals killed after 60 (4/10) and 90(1/10) days. Similar lesions were found in only a small proportion of control animals (2/23) or of guinea-pigs immunized with single peak bovine insulin (3/22). Guinea-pigs immunized with homogenates of homologous and heterologous islets of Langerhans developed signs of peri-ductulitis in a high proportion of animals killed up to about 60 days after first injection (18/26). None of these animals exhibited clearly defined signs of diabetes mellitus and the incidence of induced lesions could not be correlated with levels of circulating insulin-binding antibodies.