1. Impaired insulin/IGF-1 is responsible for diabetic gastroparesis by damaging myenteric cholinergic neurones and interstitial cells of Cajal
- Author
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Guoquan Zhang, Fengqing Ji, Bo Wu, Haimei Sun, Deshan Zhou, Shu Yang, Kai Han, Tingyi Sun, and Dandan Li
- Subjects
0301 basic medicine ,Gastroparesis ,medicine.medical_treatment ,Biochemistry ,Receptor, IGF Type 1 ,Mice ,0302 clinical medicine ,Mice, Inbred NOD ,Insulin ,Insulin-Like Growth Factor I ,Research Articles ,Stem Cell Factor ,biology ,Choline acetyltransferase ,Cholinergic Neurons ,symbols ,IGF-1 ,030211 gastroenterology & hepatology ,medicine.drug ,Research Article ,medicine.medical_specialty ,Biophysics ,Choline O-Acetyltransferase ,Diabetes Complications ,03 medical and health sciences ,symbols.namesake ,Antigens, CD ,Diabetes mellitus ,Internal medicine ,Voglibose ,medicine ,Diabetic gastroparesis ,Animals ,Humans ,Molecular Biology ,Gastric emptying ,business.industry ,Muscle, Smooth ,Cell Biology ,medicine.disease ,Interstitial Cells of Cajal ,Receptor, Insulin ,Interstitial cell of Cajal ,Insulin receptor ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,biology.protein ,Myenteric cholinergic neuron ,business ,Inositol - Abstract
Diabetic gastroparesis is a common complication of diabetes mellitus (DM) that is characterized by decreased serum insulin and insulin-like growth factor-1 (IGF-1). Despite the fact that insulin treatment not glycemic control potently accelerated gastric emptying in type 1 DM patients, the role of insulin/InsR and IGF-1/IGF-1R signaling in diabetic gastroparesis remains incompletely elucidated. In the present study, type 1 DM mice were established and treated with insulin or Voglibose for 8 weeks. The gastric emptying was delayed from DM week 4 when the gastric InsR and IGF-1R were declined. Meanwhile, the gastric choline acetyltransferase (ChAT) was significantly reduced and the myenteric cholinergic neurones and their fibers were significantly diminished. The production of stem cell factor (SCF) was dramatically repressed in the gastric smooth muscles in DM week 6. TWereafter, interstitial cells of Cajal (ICC) were clearly lost and their networks were impaired in DM week 8. Significantly, compared with Voglibose, an 8-week treatment with insulin more efficiently delayed diabetic gastroparesis development by protecting the myenteric cholinergic neurones and ICC. In conclusion, diabetic gastroparesis was an aggressive process due to the successive damages of myenteric cholinergic neurones and ICC by impairing the insulin/InsR and IGF-1/IGF-1R signaling. Insulin therapy in the early stage may delay diabetic gastroparesis.
- Published
- 2017