Diabetes in the rat is associated with a reversible postreceptor defect in cholecystokinin action
Diabetes in the rat is associated with a selective decrease in the sensitivity of pancreatic acini to the secretagogue cholecystokinin. In these animals the concentration of cholecystokinin-33 that maximally stimulates amylase release from isolated pancreatic acini shifts from 300 pM in normal animals to 1 nM in animals made diabetic with streptozotocin. To evaluate the role of the cholecystokinin receptor in this loss of sensitivity, specific 125I-cholecystokinin-33 binding to its receptors on acini was measured. When compared with controls, acini from diabetic rats bound more cholecystokinin at all hormone concentrations. In diabetes, the total cholecystokinin binding capacity of acini increased from 157 fmol/mg to 362 fmol/mg acinar protein. Moreover, the amount of cholecystokinin bound at a maximally stimulating cholecystokinin concentration increased fourfold from 11 to 44 fmol/mg acinar protein. When diabetes was reversed by treatment with insulin, both the altered secretory responses and the increased binding of 125I-cholecystokinin returned to normal. These data indicate, therefore, that the decreased sensitivity of pancreatic acini from diabetic rats is due to an impaired ability of receptor bound cholecystokinin to initiate its cellular response.
- Research Organization:
- Cell Biology Research Laboratory, Harold Brunn Institute, Mount Zion Hospital and Medical Center, San Francisco, California
- OSTI ID:
- 6310287
- Journal Information:
- Gastroenterology; (United States), Journal Name: Gastroenterology; (United States) Vol. 87:4; ISSN GASTA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMYLASE
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL MODELS
BODY
DAYS LIVING RADIOISOTOPES
DIABETES MELLITUS
DIGESTIVE SYSTEM
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE DISEASES
ENDOCRINE GLANDS
ENZYMES
GLANDS
GLYCOSYL HYDROLASES
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KININS
MAMMALS
METABOLIC DISEASES
NUCLEI
O-GLYCOSYL HYDROLASES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PANCREAS
PATHOGENESIS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RATS
RECEPTORS
RODENTS
SENSITIVITY
TRACER TECHNIQUES
VERTEBRATES