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

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.

A Close Relationship Between Networks of Interstitial Cells of Cajal and Gastrointestinal Transit In Vivo

“…Previous studies suggested that loss of ICC-MP is associated with many GI motility disorders such as diabetic gastroparesis, ulcerative colitis, and ileus ( Choi et al, 2008 ; Kaji et al, 2018 ; Lu et al, 2019 ). In addition, recent reports have shown that increased ICC-MP are associated with rapid gastric emptying, which is often observed in diabetes ( Hayashi et al, 2017 ; Kishi et al, 2019 ). The present study conclusively showed that GI transit was strongly influenced by ICC-MP networks in vivo .…”

“…Gastric emptying in mice was evaluated using the 13 C-octanoic acid breath test according to previous studies ( Creedon et al, 2013 ; Kishi et al, 2019 ). In preparation for this test, mice were fasted for 18 h. The test meal was 200 mg of a solid meal consisting of heated egg yolk and 0.2 μL 13 C-octanoic acid (Cambridge Isotope Laboratories, Inc., MA, United States).…”

“…The half-life ( T 1/2 ; min) was calculated from the slope of the elimination phase in the Δ 13 C curve. These parameters for the evaluation of gastric emptying were calculated according to previous reports ( Kishi et al, 2019 ; Matsumoto et al, 2008 ).…”

“…Immunohistochemical staining was performed to assess networks of ICC and neurons, as described in previous reports ( Kishi et al, 2019 ). Fixed whole-mount preparations were incubated with 2% bovine serum albumin in TBS to reduce nonspecific binding.…”

An Apriori Algorithm-Based Association Rule Analysis to Identify Acupoint Combinations for Treating Diabetic Gastroparesis

“…Wide glycemic fluctuations and impact on quality of life are also noticed in DGP patients [3,4]. e possible pathogenesis of DGP includes multiple factors, such as vagus neuropathy, abnormal myenteric neurotransmission, damage of inhibitory neuronal function, and the impaired function of smooth muscle cells and interstitial Cajal cells (ICCs) [5][6][7]. e suggested treatment for DGP depends on the severity.…”