Gastrointestinal dysfunction in diabetic rats relates with a decline in tissue l-arginine content and consequent low levels of nitric oxide

Umathe, Sudhir N.; Kochar, Nitin I.; Jain, Nishant; Dixit, Pankaj

doi:10.1016/j.niox.2008.10.007

Cited by 19 publications

(9 citation statements)

References 23 publications

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“…Diabetes was induced in the animals following the method described by Umathe et al [18]. After 3 weeks of being on HFD, the experimental animals were administered intraperitoneal injection of streptozotocin (STZ) dissolved in 0.1M citrate buffer, pH 4.4 at 40 mg/kg dose after 13 h of food and water fast.…”

Section: Induction Of Diabetes Mellitusmentioning

confidence: 99%

Neuroprotective and memory-enhancing effects of methanolic leaf extract of Peristrophe bicalyculata in rat model of type 2 diabetes mellitus.

Njan

Adenuga

Ajayi

et al. 2020

Heliyon

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This study investigated the effect of methanolic leaf extract of Peristrophe Bicalyculata (MEPb) on type 2 diabetes mellitus (T2DM) associated cognitive decline in Wistar rats.36 male rats weighing 130-200 g were assigned into 6 groups (n ¼ 6) as follows: normal control, diabetic control, pioglitazone-treated diabetic and three MEPb-treated diabetic groups, type 2 diabetes mellitus was induced with low dose streptozocin (STZ) injection following 3 weeks of high fat diet (HFD) intake. Thirty days after diabetes induction, rats exhibited marked and persistent hyperglycemia, animals were treated with MEPb (50, 100 and 200 mg/kg) and pioglitazone (10 mg/kg) as standard. Morris water maze (MWM) test and Novel object recognition test (NORT) were used to assess learning and memory. Blood glucose level, oxidative stress makers, pro-inflammatory marker and acetylcholinestarase activities were analysed.Both MEPb and pioglitazone significantly (P < 0.05) reduced escape latency in treated animals compared to the diabetic control group in the MWM test. Methanolic leaf extract of Peristrophe bicalyculata and pioglitazone also significantly (P < 0.05) increased discrimination index in treated animals compared to the diabetic control group in the novel object recognition test. Serum, brain and liver MDA levels were significantly (P < 0.05) decreased in MEPb and pioglitazone treated rats compared to diabetic control. Serum and liver GSH as well as CAT levels were significantly (P < 0.05) increased while brain GSH and CAT levels shows apparent increase in MEPb and pioglitazone treated rats compared with diabetic control. Treatment with MEPb caused a significant (P < 0.05) decrease in brain nitrite level, interleukin 6 and acetylcholinesterase activity compared to diabetic control group.We conclude that Methanolic leaf extract of Peristrophe bicalyculata enhanced antioxidant capacity and prevented neuroinflammation, consequently improving brain neuronal cholinergic function in experimental animals.

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Section: Induction Of Diabetes Mellitusmentioning

confidence: 99%

Neuroprotective and memory-enhancing effects of methanolic leaf extract of Peristrophe bicalyculata in rat model of type 2 diabetes mellitus.

Njan

Adenuga

Ajayi

et al. 2020

Heliyon

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show abstract

“…Treatment of diabetic rats with exogenous L-arginine normalized intestinal L-arginine content suggesting that transport of the amino acid into neurons was not impaired in diabetic intestine (Umathe et al, 2009). In diabetic animals, decreased nNOS mRNA and protein expression (Cellek et al, 2003; Shotton and Lincoln, 2006; Surendran and Kondapaka, 2005; Takahashi et al, 1997; Watkins et al, 2000; Zandecki et al, 2008), as well as impaired nerve-stimulated NANC relaxations (Jenkinson and Reid, 1995; Kaputlu et al, 1999; Martinez-Cuesta et al, 1995; Takahashi et al, 1997; Watkins et al, 2000; Zandecki et al, 2008) and low tissue nitrite levels (Umathe et al, 2009) have been reported. In STZ- guinea pigs, there were similar numbers of myenteric neurons containing nNOS in control and diabetic ilea, yet weaker fluorescent intensities of nNOS-ir nerve processes in diabetic ileum (LePard, 2005), as well as reduced generation of NO by NOS as inferred from weaker L-arginine-induced smooth muscle relaxation of diabetic ileum (Fig.…”

Section: Discussionmentioning

confidence: 99%

Neostigmine-induced contraction and nitric oxide-induced relaxation of isolated ileum from STZ diabetic guinea pigs

Cellini

Jukic

LePard

2011

Autonomic Neuroscience

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Both delayed gastrointestinal transit and autonomic neuropathy have been documented in patients with diabetes mellitus. The mechanism of neostigmine, an agent that mimics release of acetylcholine from autonomic neurons by prokinetic agents, to contract smooth muscle, despite dysfunctional enteric neural pathways, was determined using isolated ilea from STZ-treated and control guinea pigs. Both bethanechol- and neostigmine-induced contractions were stronger in diabetic ileum. Bethanechol-induced contractions of control but not diabetic ileum were increased by low dose scopolamine suggesting reduced activation of presynaptic muscarinic autoreceptors in diabetic ileum. The muscarinic receptor antagonist 4-DAMP strongly, but the nicotinic receptor antagonist hexamethonium only weakly, reduced neostigmine-induced contractions of control and diabetic ilea. The amount of acetylcholine, inferred from tissue choline content, was increased in diabetic ileum. Nicotinic neural and noncholinergic postjunctional smooth muscle receptors contributed more strongly to neostigmine-induced contractions in diabetic than control ileum. Relaxation of diabetic ileum by exogenous nitric oxide generated from sodium nitroprusside was comparable to control ileum, but smooth muscle relaxation by L-arginine using neuronal nitric oxide synthase to generate nitric oxide was weaker in diabetic ileum with evidence for a role for inducible nitric oxide synthase. Despite autonomic neuropathy, neostigmine strongly contracted ileum from diabetic animals but by a different mechanism including stronger activation of postjunctional muscarinic receptors, greater synaptic acetylcholine, stronger activation of noncholinergic excitatory pathways, and weaker activation of inhibitory pathways. A selective medication targeting a specific neural pathway may more effectively treat disordered gastrointestinal transit in patients with diabetes mellitus.

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“…In the physiological condition, NPspGC-cGMP or NO-sGC-cGMP signal pathways play an inhibitory regulation role in gastrointestinal smooth muscle motility. Recently, it was demonstrated that diabetesinduced L-arginine deficiency and consequent low levels of NO in gastrointestinal tissues could be possible causes for the gastrointestinal dysfunction, and L-arginine supplementation can prevent this [32]. Whether the NPs-pGCcGMP signal pathway upregulation is possibly a compensatory response to diabetes-induced L-arginine deficiency and consequent low levels of NO in gastrointestinal tissues is still uncertain.…”

Section: Discussionmentioning

confidence: 99%

Natriuretic Peptide-Dependent cGMP Signal Pathway Potentiated the Relaxation of Gastric Smooth Muscle in Streptozotocin-Induced Diabetic Rats

Liu

Cai

et al. 2009

Dig Dis Sci

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A common gastrointestinal complication of diabetes is gastroparesis, and patients with gastroparesis may present with early satiety, nausea, vomiting, bloating, postprandial fullness, or upper abdominal pain. However, the pathogenesis is not clear yet. A recent study indicated that atrial natriuretic peptide (ANP) was secreted from the gastric mucosa and the ANP family plays an inhibitory role in the regulation of gastrointestinal motility, but the effect of the natriuretic peptide signal pathway on diabetic gastroparesis has not been reported. The study investigated the effect of C-type natriuretic peptide (CNP) particulate guanylyl cyclase (pGC) cyclic guanosine monophosphate (cGMP) signaling on gastroparesis in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into two groups; group I: normal control rats; group II: STZ-induced diabetic rats; 4 weeks after induction, the experiments were performed. The spontaneous contraction of gastric smooth muscle strips was recorded by using physiographs in control and diabetic rats. The pGC activity in response to CNP and cGMP production in gastric smooth muscle were measured by using radioimmunoassay (RIA) in normal and diabetic rats. CNP induced a longer lasting relaxation of gastric antral circular smooth muscle strips in STZ-induced diabetic rats. The inhibitory effect of CNP on spontaneous contraction revealed a dose-dependency, and the inhibitory percentages were 25.5 +/- 1.7%, 43.6 +/- 3.2%, 85.1 +/- 2.5% in diabetic rats and 20.5 +/- 1.5%, 31.1 +/- 1.7%, 58.9 +/- 3.7% in the control group at the concentrations of 0.01, 0.03, and 0.1 mumol/l, respectively. The cGMP production and pGC activity in response to CNP in gastric muscle tissues were significantly potentiated in STZ-induced diabetic rats. Natriuretic peptide receptor type B (NPR-B) gene was expressed in the gastric smooth muscles of normal and diabetic rats, and the expression was increased in diabetic rats. The results suggest that natriuretic peptide-dependent pGC-cGMP signal is upregulated and may contribute to diabetic gastroparesis in STZ-induced diabetic rats.

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Gastrointestinal dysfunction in diabetic rats relates with a decline in tissue l-arginine content and consequent low levels of nitric oxide

Cited by 19 publications

References 23 publications

Neuroprotective and memory-enhancing effects of methanolic leaf extract of Peristrophe bicalyculata in rat model of type 2 diabetes mellitus.

Neuroprotective and memory-enhancing effects of methanolic leaf extract of Peristrophe bicalyculata in rat model of type 2 diabetes mellitus.

Neostigmine-induced contraction and nitric oxide-induced relaxation of isolated ileum from STZ diabetic guinea pigs

Natriuretic Peptide-Dependent cGMP Signal Pathway Potentiated the Relaxation of Gastric Smooth Muscle in Streptozotocin-Induced Diabetic Rats

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