Reversible impairment of glucose-induced insulin secretion in SHR/N-cp rats. Genetic model of type II diabetes.
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)
Voyles
N R
NR
Diabetes Research Laboratory, Veterans Administration Medical Center, Washington, DC 20422.
Powell
A M
AM
Timmers
K I
KI
Wilkins
S D
SD
Bhathena
S J
SJ
Hansen
C
C
Michaelis
O E
OE
Recant
L
L
D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D004195:Disease Models, Animal; D005215:Fasting; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009765:Obesity / Q000097:blood; D010179:Pancreas / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR / Q000097:blood* / Q000235:genetics; D011919:Rats, Inbred Strains / Q000097:blood*; D013395:Sucrose / Q000008:administration & dosage; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D013395:Sucrose; D001120:Arginine