The Role of Prostaglandins in Disrupted Gastric Motor Activity Associated With Type 2 Diabetes

Autor: Kenton M. Sanders, Matthew C. Shonnard, Lauren E. Peri, Sung Jin Hwang, Peter J. Blair, Yulia Bayguinov, Sean M. Ward
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Blood Glucose
medicine.medical_specialty
Complications
Endocrinology
Diabetes and Metabolism
Gastric motility
Prostaglandin
030209 endocrinology & metabolism
Type 2 diabetes
Motor Activity
Real-Time Polymerase Chain Reaction
Diabetes Mellitus
Experimental
03 medical and health sciences
chemistry.chemical_compound
symbols.namesake
Mice
0302 clinical medicine
Downregulation and upregulation
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
Animals
Humans
Gastroparesis
business.industry
Enteric neuropathy
Blood Glucose Self-Monitoring
medicine.disease
Immunohistochemistry
Interstitial cell of Cajal
Electrophysiology
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
chemistry
Diabetes Mellitus
Type 2
Cyclooxygenase 2
symbols
Prostaglandins
business
Signal Transduction
Zdroj: Diabetes
ISSN: 1939-327X
0012-1797
Popis: Patients with diabetes often develop gastrointestinal motor problems, including gastroparesis. Previous studies have suggested this gastric motor disorder was a consequence of an enteric neuropathy. Disruptions in interstitial cells of Cajal (ICC) have also been reported. A thorough examination of functional changes in gastric motor activity during diabetes has not yet been performed. We comprehensively examined the gastric antrums of Lepob mice using functional, morphological, and molecular techniques to determine the pathophysiological consequences in this type 2 diabetic animal model. Video analysis and isometric force measurements revealed higher frequency and less robust antral contractions in Lepob mice compared with controls. Electrical pacemaker activity was reduced in amplitude and increased in frequency. Populations of enteric neurons, ICC, and platelet-derived growth factor receptor α+ cells were unchanged. Analysis of components of the prostaglandin pathway revealed upregulation of multiple enzymes and receptors. Prostaglandin-endoperoxide synthase-2 inhibition increased slow wave amplitudes and reduced frequency of diabetic antrums. In conclusion, gastric pacemaker and contractile activity is disordered in type 2 diabetic mice, and this appears to be a consequence of excessive prostaglandin signaling. Inhibition of prostaglandin synthesis may provide a novel treatment for diabetic gastric motility disorders.
Databáze: OpenAIRE
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