Hyperglycemia in the early stages of type 1 diabetes accelerates gastric emptying through increased networks of interstitial cells of Cajal

PLoS One. 2019 Oct 9;14(10):e0222961. doi: 10.1371/journal.pone.0222961. eCollection 2019.

Abstract

Gastric emptying (GE) can be either delayed or accelerated in diabetes mellitus (DM). However, most research has focused on delayed GE mediated by a chronic hyperglycemic condition in DM. As such, the function of GE in the early stages of DM is not well understood. Interstitial cells of Cajal (ICC) are pacemaker cells in the gastrointestinal tract. In the present study, we investigated changes in GE and ICC networks in the early stages of DM using a streptozotocin-induced type 1 diabetic mouse model. The changes in GE were measured by the 13C-octanoic acid breath test. ICC networks were immunohistochemically detected by an antibody for c-Kit, a specific marker for ICC. Our results showed that GE in type 1 DM was significantly accelerated in the early stages of DM (2-4 weeks after onset). In addition, acute normalization of blood glucose levels by a single administration of insulin did not recover normal GE. ICC networks of the gastric antrum were significantly increased in DM and were not affected by the acute normalization of blood glucose. In conclusion, our results suggest that GE is accelerated in the early stages of DM, and it is associated with increased ICC networks. This mechanism may help to clarify a link between the onset of DM and GE disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / physiopathology
  • Disease Models, Animal
  • Gastric Emptying*
  • Hyperglycemia / blood
  • Hyperglycemia / complications*
  • Hyperglycemia / physiopathology
  • Insulin / pharmacology
  • Insulin / therapeutic use
  • Interstitial Cells of Cajal / pathology*
  • Male
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins c-kit / metabolism
  • Streptozocin

Substances

  • Blood Glucose
  • Insulin
  • Streptozocin
  • Proto-Oncogene Proteins c-kit

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology (24248050 to M.H. and 18K14604 to N.K.). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.