Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat.
Hyperglycemia has a profound effect on gastric motility. However, little is known about the site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose-clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg/dl had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg/dl), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10(-5) M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT(3) antagonist, 0.5 g/kg) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, N(G)-nitro-L-arginine methyl ester (L-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia and, in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation.
Zhou
Shi-Yi
SY
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Lu
Yuan-Xu
YX
Owyang
Chung
C
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002211:Capsaicin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D010134:Fenclonine / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D017829:Granisetron / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000503:physiopathology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors
D001786:Blood Glucose; D002211:Capsaicin; D002217:Carbachol; D010134:Fenclonine; D005947:Glucose; D017829:Granisetron; D018738:Hexamethonium; D006727:Hormone Antagonists; D019331:NG-Nitroarginine Methyl Ester; D014660:Vasoactive Intestinal Peptide; C048507:vasoactive intestinal peptide, 4-chloro-Phe(6)-Leu(17)-