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D C Whitcomb

Publications and source records attributed to D C Whitcomb.

79 records · Page 5Linked to original sources
PubMed1991

Insulin-sparing effects of pancreatic polypeptide in congenitally obese rodents.

Chronic treatment with bovine pancreatic polypeptide (bPP) is reported to decrease body weight and reduce fasting glucose and insulin concentrations in congenitally obese mice. The present study examines the effects of acute and chronic bPP treatment on insulin release and glucose clearance in lean and obese rodents. After single injections of 0, 5, 50, or 500 micrograms of bPP/kg of body weight, the insulin response to an intragastric glucose meal (5 g/kg of body weight) was substantially inhibited by the two higher doses of bPP. The change in glucose concentration over time was similar among all animals except those receiving the highest dose of bPP (500 micrograms/kg of body weight); in this group, glucose rose to higher levels and was slower to return to basal levels. Chronic treatment of rats with 200 micrograms of bPP/day/kg of body weight for 5 days did not modify glucose or insulin responses to the glucose meal, but did increase the activity of hepatic glycogen synthetase. In contrast, basal glucose levels were lower in obese mice (ob/ob) treated with bPP and glucose clearance was improved in the treated group after injection of exogenous insulin. Islet hormone concentrations in pancreatic extracts were compared in lean and obese mice treated with and without 200 micrograms of bPP/day/kg of body weight for 5 days. The pancreases of obese mice had higher concentrations of insulin and PP, and treatment with exogenous bPP increased endogenous PP in the pancreases of both phenotypes. Treatment with exogenous bPP also increased the insulin content of obese pancreases, but was without effect in pancreases of lean mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Characterization of saturable binding sites for circulating pancreatic polypeptide in rat brain.

Pancreatic polypeptide (PP) inhibits pancreatic exocrine secretion by indirect mechanisms that may be centrally mediated. The central site of action of PP that results in inhibition of pancreatic secretion has not been identified. Using autoradiography to identify 125I-PP binding to frozen sections of rat brain, we have identified saturable, high-affinity PP receptors in high concentrations in the interpenduncular nucleus, area postrema (AP), nucleus tractus solitarius, and dorsal motor nucleus of the vagus. The PP receptor differs from neuropeptide Y and peptide YY receptors in its binding specificity and location. Because PP is not produced in the brain, and the blood-brain barrier (BBB) excludes circulating peptides from most areas in the brain, we employed an in vivo radioreceptor assay to determine whether circulating PP binds to areas such as the AP that has both an incomplete BBB and a high concentration of PP receptors. 125I-PP and 131I-bovine serum albumin were infused simultaneously into rats through a peripheral vein with or without excess unlabeled PP. After 10 min, rats were killed and the brains were removed and cut into eight regions based on the autoradiographic localization of PP receptors. There was a significant (P less than 0.02) increase in saturable radiolabeled PP accumulation in the region that included the AP, demonstrating that circulating PP can bind to this area of the brain in vivo. PP is released into the circulation after a meal via mechanisms that exhibit vagal and cholinergic dependence. We speculate that PP completes a feedback loop by binding to receptors in the AP and interacting with the adjacent vagal nuclei to inhibit vagal activity.

Animals↗
PubMed1989

Marked QRS complex abnormalities and sodium channel blockade by propoxyphene reversed with lidocaine.

The opiate analgesic propoxyphene produces cardiac toxicity when taken in overdose. We recently observed a patient with propoxyphene overdose in whom marked QRS widening was reversed by lidocaine. The reversal is apparently paradoxical as both agents block the inward sodium current (INa). We examined possible mechanisms of the reversal by measuring INa in rabbit atrial myocytes during exposure to propoxyphene and the combination of propoxyphene and lidocaine (60 and 80 microM, respectively). Propoxyphene caused use-dependent block of INa during pulse train stimulation. Block recovered slowly with time constants of 20.8 +/- 3.9 s. Block during lidocaine exposure recovered with time constants of 2-3 s. During exposure to the mixture, block recovered as a double exponential. The half time for recovery during exposure to the mixture was 1.6 +/- .9 s compared with a half-time of 14.3 +/- 2.9 s during exposure to propoxyphene alone. During pulse train stimulation, less steady-state block was observed during exposure to the mixture than during exposure to propoxyphene alone when the interval between pulses was greater than 0.95 s. Both drugs compete for a common receptor during the polarizing phase. The more rapid dissociation of lidocaine during the recovery period leads to less block during the mixture than during exposure to propoxyphene alone. The experiments suggest a mechanism for reversal of the cardiac toxicity of drugs which have slow unbinding kinetics.

Adult↗
PubMed1985

Theoretical basis for a new in vivo radioreceptor assay for polypeptide hormones.

To date the in vivo identification and quantitation of specific hormone receptors has been difficult, time consuming, and lacking in sensitivity. We present the theory underlying a new in vivo radioreceptor assay for polypeptide hormones based on receptor theory derived from in vitro investigations and in vivo kinetic and autoradiographic studies. The assay was developed from a tissue model and a theory of hormone distribution. Measuring the labeled hormone distributed between the plasma and interstitial space in the presence or absence of excess unlabeled hormone permits the accurate determination of hormone specifically bound to receptors. This approach eliminates the problem of nonspecific binding due to free tracer, hormone degradation products, or labeled non-hormone molecules. A receptor compartment and specific binding of hormone are calculated from only four measured parameters: total tissue labeled hormone, tissue albumin, plasma labeled hormone, and plasma albumin. The method is applicable to most tissues and hormones under a variety of conditions and permits simultaneous comparison of multiple tissues in the same animal under identical conditions.

Albumins↗
PubMed1985

Identification of tissue insulin receptors: use of a unique in vivo radioreceptor assay.

An in vivo radioreceptor assay for polypeptide hormones has been developed and applied to the identification of tissue insulin receptors. The theoretical basis for this assay is presented elsewhere in this issue. 125I-insulin and 131I-albumin were infused into male rats with increasing amounts of unlabeled insulin. Plasma samples were taken at 1-min intervals until the animals were killed at 5 min. Tissue samples were excised and weighed and the activity due to each isotope counted. By comparing the differential distribution of the labeled tracers and applying the results to a compartment model, the specific, displaceable binding of insulin to tissue receptors could be demonstrated. Binding was detected in the liver, muscle, fat, adrenal glands, pancreas, small intestines, and spleen.

Adrenal Glands↗