Effects of Diabetes mellitus on the Contractile Activity of Carbachol and Galanin in Isolated Gastric Fundus Strips of Rats

Korolkiewicz, Roman; Rekowski, Piotr; Szyk, Agnieszka; Kato, Shinichi; Yasuhiro, Tetsuya; Kubomi, Masafumi; Tashima, Kimihito; Takeuchi, Koji

doi:10.1159/000028227

Cited by 17 publications

(8 citation statements)

References 37 publications

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“…In our study, diabetic rats had considerably higher NOx plasma levels than their age-matched, healthy littermates which is not surprising, as an almost 100% increase in NOx blood plasma level has been described in rats, 6 weeks after STZ injection [29]. Although the reports of NOS activity in diabetic gastric mucosa are scarce and conflicting [24, 30], we demonstrated an increase of total NOS and iNOS activities in gastric corpus mucosa of starved and cold-stressed diabetic animals, the results being consistent in part with our previous work [31]. Thus, it was not unexpected that NOx output in the gastric juice was augmented in diabetic rats as stress, during which stomach is one of the target organs, stimulates NO release [32].…”

Section: Discussionsupporting

confidence: 92%

Increased Susceptibility of Diabetic Rat Gastric Mucosa to Food Deprivation during Cold Stress

Korolkiewicz

Tashima²,

Kubomi³

et al. 1999

Digestion

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Background: We investigated the mechanisms responsible for the increased susceptibility of diabetic rat gastric mucosa to damage inflicted by overnight food deprivation (18 h) and its worsening by the cold restraint stress (4°C, 3 h). Methods: Gastric damage was measured in fasted animals, some of which were rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ; 70 mg/kg) 5 weeks before experiments (STZ 5W). Results: STZ 5W rodents showed a number of hemorrhagic lesions in corpus mucosa (26.8 ± 5.2 mm²) which could be prevented by insulin or nitric oxide synthase (NOS) inhibitors: aminoguanidine or L-NAME (N^ω-nitro-L-arginine methyl ester). Mucosal injury was further aggravated by low temperature (51.1 ± 7.8 mm²), the damage ameliorated by insulin, aminoguanidine, or L-NAME. The salutary actions of L-NAME were L-arginine sensitive. Low temperature and L-NAME did not significantly influence the gastric secretory parameters in normal rats. On the other hand, L-NAME and aminoguanidine counteracted the attenuation of gastric juice acidity and acid output in STZ 5W rodents. Blood plasma nitrite and nitrate levels and outputs in gastric juice were augmented in STZ 5W animals in comparison to controls. The total activities of NOS including inducible NOS but not constitutive NOS were markedly enhanced by fasting and cold restraint in gastric mucosa of STZ 5W animals (2.2- and 3.7- or 2.4- and 17.9-fold respectively). Conclusions: Stressful stimuli, such as food bereavement and cold challenge contribute to the elevated susceptibility of diabetic gastric mucosa to damage, even though the main aggressive factor, i.e., gastric acid secretion, is attenuated. The enhanced production of nitric oxide by inducible NOS during food deprivation and cold exposure seems to play an important role in gastric mucosal integrity disturbances during diabetes.

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Section: Discussionsupporting

confidence: 92%

Increased Susceptibility of Diabetic Rat Gastric Mucosa to Food Deprivation during Cold Stress

Korolkiewicz

Tashima²,

Kubomi³

et al. 1999

Digestion

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“…Abnormal neural innervation and neurotransmission of both inhibitory and excitatory neurotransmitters, interstitial cells of Cajal, and muscle function have been described (25,30,36). Smooth muscle dysfunction has been previously suggested in streptozotocin-induced diabetic models (16,33).…”

Section: Discussionmentioning

confidence: 98%

Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation

James¹,

Ryan²,

Crowell³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation. Am J Physiol Gastrointest Liver Physiol 287: G612-G619, 2004. First published April 23, 2004 10.1152/ ajpgi.00431.2003.-The C57BLKS/J db/db mouse develops hyperglycemia and has delayed gastric emptying that is improved with tegaserod, a partial 5-HT4 agonist. Our aims here were to determine regional gastric contractility alterations in C57BLKS/J db/db mice and to determine the effects of serotonin and tegaserod. The contractile effects of bethanechol, serotonin, and tegaserod in fundic, antral, and pyloric circular muscle were compared in C57BLKS/J db/db mice and normal littermates. The effects of tetrodotoxin, atropine, and 5-HT receptor antagonists were studied. Contractions in response to bethanechol were decreased in the fundus, similar in the antrum, but increased in the pylorus in diabetic mice compared with controls. Serotonin and, to a lesser extent, tegaserod caused contractions that were more pronounced in the fundus than in the antrum and pylorus in both diabetic and normal mice. Serotonin-induced contractions were partially inhibited by atropine, the 5-HT4 antagonist GR113808, and the 5-HT2 antagonist cinanseron but not tetrodotoxin. Regional gastric contractility alterations are present in this diabetic gastroparesis mouse model. Fundic contractility was decreased, but pyloric contractility was increased in the pylorus to cholinergic stimulation in diabetic mice. Serotonin's contractile effect is mediated, in part, through muscarinic, 5-HT2, and 5-HT4 receptors. This study suggests that fundic hypomotility and pyloric hypercontractility, rather than antral hypomotility, play important roles for the gastric dysmotility that occurs in diabetes.serotonin; tegaserod GASTROPARESIS (delayed gastric emptying) is frequent in diabetic patients. It is a well-recognized complication of longstanding diabetes. Although classically, gastroparesis occurs in insulin-dependent diabetic patients, it also develops in type 2 (T2DM) or non-insulin-dependent diabetes mellitus (15). Gastroparesis is associated with antral hypomotility and perhaps pyloric dysfunction (2, 23).Treatment of gastroparesis is with prokinetic agents, which accelerate gastric emptying. Tegaserod, an aminoguanidine indole compound, is a recently developed 5-HT 4 partial agonist (1). Activation of 5-HT 4 receptors triggers the release of neurotransmitters from the enteric nerves resulting in increased contractility and stimulation of the peristaltic reflex (10). Tegaserod has been shown to accelerate gastric emptying in some (6) but not all studies (28).Strains of rats and mice with spontaneously developing hyperglycemia have been recognized as useful models to study the effects of diabetes. The Jackson Laboratory C57BLKS/J db/db mouse spontaneously develops hyperglycemia (12) and is a model for non-insulin-dependent diabetes mellitus (24). Prior studies in this mouse strain (22) have shown delayed gastric em...

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“…Hence, in fundus, both neostigmine-induced contractions (Fig. 4) and carbachol-induced contractions (Korolkiewicz et al, 1998) were decreased in diabetic animals. Since carbachol and neostigmine had similar effects, data suggest that in fundus, diabetes did not alter the rate of endogenous Ach breakdown by AchE.…”

Section: Discussionmentioning

confidence: 83%

“…Carbachol activates both muscarinic and nicotinic receptors but is resistant to breakdown by AchE. In diabetic animals, maximal contractions to carbachol were decreased in fundus (Korolkiewicz et al, 1998) and corpus (Takahashi et al, 1996), but increased in antrum (Maruyama et al, 1999). Hence, in fundus, both neostigmine-induced contractions (Fig.…”

Section: Discussionmentioning

confidence: 99%

Regional differences in neostigmine-induced contraction and relaxation of stomach from diabetic guinea pig

Cellini

DiNovo

Harlow

et al. 2011

Autonomic Neuroscience

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Delayed gastric emptying and autonomic neuropathy have been documented in patients with diabetes mellitus. Some medications used to treat delayed gastric emptying enhance release of acetylcholine from autonomic neurons to strengthen gastric contractions. Autonomic coordination among gastric regions may be altered in diabetes resulting in poor outcomes in response to prokinetic drugs. Fundus, antrum, and pylorus from STZ or control guinea pigs were treated with neostigmine to mimic release of acetylcholine from autonomic neurons by prokinetic agents. In diabetic animals, neostigmine-induced contractions were weaker in fundus and pylorus but similar in antrum. The muscarinic receptor antagonist 4-DAMP or the nicotinic receptor antagonist hexamethonium reduced neostigmine-induced contractions. Activation of presynaptic muscarinic receptors on nitrergic neurons was impaired in fundus and antrum from diabetic animals. Nerve-stimulated contractions and relaxations, number of nNOS myenteric neurons, and tissue choline content were reduced in fundus from diabetic animals. Despite reduced number of myenteric neurons, tissue choline content was increased in antrum from diabetic animals. Since cholinergic motility of each gastric region was affected differently by diabetes, prokinetic drugs that nondiscriminately enhance acetylcholine release from autonomic neurons may not effectively normalize delayed gastric emptying in patients with diabetes and more selective medications may be warranted.

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Effects of Diabetes mellitus on the Contractile Activity of Carbachol and Galanin in Isolated Gastric Fundus Strips of Rats

Cited by 17 publications

References 37 publications

Increased Susceptibility of Diabetic Rat Gastric Mucosa to Food Deprivation during Cold Stress

Increased Susceptibility of Diabetic Rat Gastric Mucosa to Food Deprivation during Cold Stress

Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation

Regional differences in neostigmine-induced contraction and relaxation of stomach from diabetic guinea pig

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