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.
Highlights
Diabetes mellitus (DM) is the leading dismetabolic chronic disease with a global prevalence approaching 400 million people [1]
Type 1 DM mouse model was successfully made by an injection of Alloxan monohydrate, which resulted in apparent declines in the serum insulin by 62.2–78.9% and insulin-like growth factor-1 (IGF-1) by 12.1–43.8% from as early as DM week 2
The amplitude of gastric muscle contraction was decreased but the frequency of the gastric muscle contraction was increased in DM week 4, which may be due to compensation for the gastric movement
Summary
Diabetes mellitus (DM) is the leading dismetabolic chronic disease with a global prevalence approaching 400 million people [1]. The diabetic gastroparesis is not malignant, it inhibits absorption of nutrients and oral antidiabetic medicine, which could interfere with glycemic control and lead to an inefficient treatment of DM. The pathogenesis of the diabetic gastroparesis is still under research and it is believed to be multifactorial, e.g. hyperglycemia, enteric nervous system (ENS) injury, myopathy, loss of interstitial cells of Cajal (ICC) etc. There have been substantial advancement in our understanding of the underlying cellular dysfunction of the diabetic gastroparesis, how the ENS and ICC are damaged in diabetic gastroparesis remain poorly known
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