HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bianco, A. Articles by Ghirlanda, G. Search for Related Content PubMed PubMed Citation Articles by Bianco, A. Articles by Ghirlanda, G. Social Bookmarking                What's this?

Effect of Sildenafil on Diabetic Gastropathy

¹ Medicina Interna, Università Cattolica, Rome, Italy
² Medicina Nucleare, Università Cattolica, Rome, Italy

Diabetic gastropathy (DG) is the most serious neuromuscular dysfunction of the stomach that may affect diabetic patients. DG is a syndrome of delayed gastric emptying correlated to alterations of gastric tone, contractility, and myoelectrical activity. Gastric dysrhythmias, antral hypomotility, antral dilation, antroduodenal incoordination, and pylorospasm variously relate to DG.

DG pathogenesis is multifactorial: autonomic neuropathy, microangiopathy, and the degenerative impairment of gastric neuromuscular structure are possible mechanisms of gastric dysfunction. Also, the acute increase in blood glucose might reversibly delay gastric emptying (1,2). Gastric dysrhythmias correlate with a disturbance of gastric electrical slow waves (ESWs). ESW rhythm, which is generated by interstitial cells of Cajal, coordinates gastric peristalsis (3,4). Cajal cells, distributed in specific locations within the enteric tunica muscolaris, serve as electrical pacemakers and mediators of neuromuscolar transmission (5).

These cells have close relationships with neurons of myenteric plexus and are specifically responsive to nitric oxide (NO) neurotransmission through the activation of their intracellular cyclic guanosin monophosphate (cGMP), the second messenger of the nitrergic pathway (5,6). Injury or reversible impairment of gastric nitrergic neurons or of Cajal cells may alter nerve-muscle communications. In this sense, reduced NO-dependent neurotransmission might be crucial in the loss of coordinated mechanical smooth muscle response in diabetic patients. Sildenafil, a drug that inhibits phosphodiesterase type 5 (PD-5)-mediated cGMP breakdown, might increase cGMP of Cajal cells when the signal linked to NO is low. It is conceivable that in DG, sildenafil could improve gastric emptying by reversing the loss of nitrergic neurotransmission, as already demonstrated in animal models (7).

We recently observed two patients with DG and evaluated a new therapeutic approach to gastric emptying using sildenafil. Two type 1 diabetic females, aged 45 and 40 years and not pregnant, were hospitalized for acute diabetic gastroparesis with early satiety and postprandial fullness, recurrent nausea, vomiting, and heartburn. A complete laboratory workup evidenced normal complete blood cell count, blood urea nitrogen, creatinine, sodium, and potassium. According to the criteria outlined by Ewing and Clarke, a total score >6 was found as index of autonomic nerve damage (8). A complete gastrointestinal radiographic and endoscopic study ruled out peptic disease or mechanical obstructions. Common prokinetic drugs did not relieve symptoms. After informed consent, both patients were evaluated by gastric scintigraphy to assess a possible therapeutic effect of sildenafil. The gastric emptying scintigraphy was perfomed three times: on the first day, without drugs, to obtain a baseline study and on the second and third days 30 min after the oral administration of two different drugs, sildenafil (50 mg tablets) or placebo (vitamin A), according to a randomization to evaluate the different effects of the drugs on gastric emptying. After an overnight fast, each subject consumed, in 5 min, a solid meal that consisted of a sandwich with two ^99mTc MAA-scrambled eggs (74 MBq) and a glass of water (9). The gastric emptying parameters examined were lag phase, which is defined as when activity first exits the stomach (10), half time in minutes, and residual activity at 120 min in percent. The improvement of gastring emptying parameters was only observed after sildenafil administration (Table 1).

Footnotes

Address correspondence to Giovanni Ghirlanda, Servizio di Diabetologia Università, Cattolica del Sacro, Cuore, Largo A. Gemelli 00168, Roma, Italy. E-mail: gghirlanda{at}rm.unicatt.it.

References

1. Rayner CK, Samson M, Jones KL, Horowitz M: Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care 24: 371–381, 2001[Abstract/Free Full Text]
   
2. Watkins PJ: The enigma of autonomic failure in diabetes. J Roy Phys London 32: 360–365, 1998
   
3. Thuneberg L: Interstitial cells of Cajal. In Handbook of Physiology. The Gastrointestinal System. Sect. 6, vol. 1. Bethesda, MD, American Physiological Society, 1989, p. 349–386
   
4. Chen JD, Lin Z, Pan J, McCallun RW: Abnormal gastric myoelectrical activity and delayed gastric emptying in patients with symptoms suggestive of gastroparesis. Dig Dis Sci 41: 1538–1545, 1996[Medline]
   
5. Ward SM: Interstitial cell of Cajal in enteric neurotransmission. Gut 40–43, 2000
   
6. Sanders KM, Ward SM: Nitric oxide as mediator of nonadrenergic noncholinergic neurotrasmission. Am J Physiol 262: G379–G382,1992[Abstract/Free Full Text]
   
7. Watkins CC, Sawa A, Jaffrey S, Blackshaw S, Barrow RK, Snyder SH, Ferris CD: Insulin restores natural nitric oxide synthase expression and function that is lost in diabetic gastropathy. J Clin Invest 106: 373–384, 2000[Medline]
   
8. Ewing DJ, Clarke BF: Diagnosis and management of diabetic autonomic neuropathy. Br Med J 285: 916–918, 1982
   
9. Siegel JA, Wu RK, Knigth LC, Zelac RE, Stern HS, Malmud LS: Radiation dose estimates for oral agents used in upper gastrointestinal disease. J Nucl Med 24: 835–838, 1983[Abstract/Free Full Text]
   
10. Chatterton BE: Nuclear Medicine in Clinical Diagnosis and Treatment. Edinburgh, Churchill Livingstone, Vol. 1. 1994, p. 393–405
    

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S Kindt and J Tack Impaired gastric accommodation and its role in dyspepsia Gut, December 1, 2006; 55(12): 1685 - 1691. [Abstract] [Full Text] [PDF]

				M. Yamaguchi, F. Nishimura, H. Naruishi, Y. Soga, S. Kokeguchi, and S. Takashiba Thiazolidinedione (Pioglitazone) Blocks P. gingivalis- and F. nucleatum, but not E. coli, Lipopolysaccharide (LPS)-induced Interleukin-6 (IL-6) Production in Adipocytes J. Dent. Res., March 1, 2005; 84(3): 240 - 244. [Abstract] [Full Text] [PDF]

				T. Saito, Y. Shimazaki, Y. Kiyohara, I. Kato, M. Kubo, M. Iida, and T. Koga The Severity of Periodontal Disease is Associated with the Development of Glucose Intolerance in Non-diabetics: The Hisayama Study J. Dent. Res., June 1, 2004; 83(6): 485 - 490. [Abstract] [Full Text] [PDF]

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bianco, A. Articles by Ghirlanda, G. Search for Related Content PubMed PubMed Citation Articles by Bianco, A. Articles by Ghirlanda, G. Social Bookmarking                What's this?