Accelerated gastric emptying of glucose in Zucker type 2 diabetic rats: role in postprandial hyperglycaemia.
Patients with early non-insulin-dependent diabetes mellitus (NIDDM) empty glucose solutions from their stomachs more rapidly than non-diabetic control subjects, and this exacerbates postprandial hyperglycaemia. To determine if accelerated gastric emptying occurred in a rat model of NIDDM and influenced postprandial hyperglycaemia, gastric emptying of glucose was measured, and the effect of slowing the gastric emptying rate on postprandial hyperglycaemia was observed. We tested eight male obese Zucker diabetic rats and eight age-matched lean Zucker controls at 10-13 weeks of age to measure gastric emptying of glucose (by gamma scintigraphy). Rats fasted overnight were gavaged with 30% glucose at 1 ml/100 g body weight. Separately, six Zucker diabetic rats and six lean controls were tested for sensitivity to the inhibitory effects of cholecystokinin and secretin on gastric emptying. The diabetic rats emptied glucose significantly faster than controls (t1/2 = 37.3 +/- 1.5 vs 58.8 +/- 2.3 min in controls), and aging exaggerated this differential. Camostat, a stimulant of cholecystokinin and secretin release, added to the glucose meal significantly slowed gastric emptying (t1/2 = 123 +/- 23 and 166 +/- 19 min, diabetic vs lean, respectively), and significantly reduced postprandial hyperglycaemia in diabetic rats. Compared to Zucker lean controls, Zucker diabetic rats were as sensitive (cholecystokinin) or more sensitive (secretin) to gastrointestinal hormones that inhibit gastric emptying. The results demonstrate accelerated gastric emptying in a rat model of NIDDM, consistant with similar observations in humans with early NIDDM. These results also support the proposal that interventions to slow gastric emptying improve glucose control in this disease.
Green
G M
GM
Department of Physiology, University of Texas Health Science Center at San Antonio 78284-7756, USA.
Guan
D
D
Schwartz
J G
JG
Phillips
W T
WT
D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004952:Esters; D016670:Gabexate / Q000031:analogs & derivatives*; D005746:Gastric Emptying / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006146:Guanidines / Q000008:administration & dosage; D006943:Hyperglycemia / Q000503:physiopathology*; D008297:Male; D019518:Postprandial Period; D051381:Rats; D011924:Rats, Zucker; D012633:Secretin / Q000008:administration & dosage; D014361:Trypsin Inhibitors / Q000008:administration & dosage
D004952:Esters; D006146:Guanidines; D014361:Trypsin Inhibitors; C034532:camostat; D012633:Secretin; D016670:Gabexate; D002766:Cholecystokinin; D005947:Glucose