Acid secretory changes in streptozotocin-diabetic rats: different responses to various secretagogues

We examined gastric acid secretion in response to various stimuli in streptozotocin (STZ) induced diabetic rats and characterized the alteration of acid secretory responses in diabetic conditions. Animals were injected STZ (70 mg/kg, intraperitoneally) and used after five weeks of diabetes with blood glucose >350 mg/dl. Under urethane anesthesia, the experiment was performed in a chambered stomach or a whole stomach preparation, and the acid secretion was measured at pH 7.0 using a pH-stat method and by adding 100 mM NaOH. The acid secretion was stimulated by intravenous infusion of either histamine (4 mg/kg/hr), pentagastrin (60 microg/kg/hr), or carbachol (20 microg/kg/hr) or by intraluminal application of peptone solution (4%), or vagal electrical stimulation (2 msec, 3 Hz, 0.5 mA). In normal rats, acid secretion was increased in response to either histamine, pentagastrin, carbachol, peptone, or electrical vagal stimulation. In STZ diabetic rats, however, changes in acid secretion varied depending on the stimuli; the acid response to histamine remained unchanged, but the responses to vagal electrical stimulation or pentagastrin and carbachol were significantly decreased or enhanced, respectively, as compared to normal rats. Likewise, the acid response to peptone was also markedly enhanced in STZ-diabetic rats, and this response was significantly blocked by atropine and YM022 (a CCKB/gastrin antagonist) as well as famotidine in both normal and diabetic rats. Both pentagastrin and carbachol increased the luminal release of histamine in normal rats, and these responses were significantly augmented in STZ-diabetic rats. The altered acid response and histamine release induced by pentagastrin in STZ diabetic rats were partially reversed by daily injection of insulin. These results suggest that STZ-diabetic rats showed different changes in gastric acid secretion in response to various stimuli. The increased acid secretory response may be associated with an enhanced release of mucosal histamine, while the decreased response may be due to vagal neuropathy.