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Altered chronic glycemic control in a clinically relevant model of rat thoracic
spinal contusion.
Authors Harris KK, Welch BA, Smith AM, Pride Y, Grayson BE
Submitted By Submitted Externally on 3/10/2023
Status Published
Journal Bioscience reports
Year 2023
Date Published 1/1/2023
Volume : Pages 43 : Not Specified
PubMed Reference 36472154
Abstract The lifetime risk for Type 2 diabetes mellitus remains higher in people with
spinal cord injuries (SCIs) than in the able-bodied population. However, the
mechanisms driving this disparity remain poorly understood. The goal of the
present study was to evaluate the impact of a palatable high-fat diet (HFD) on
glycemic regulation using a rodent model of moderate thoracic contusion. Animals
were placed on either Chow or HFD and tolerance to glucose, insulin, and ENSURE
mixed meal were investigated. Important targets in the gut-brain axis were
investigated. HFD consumption equally induced weight gain in SCI and naïve rats
over chow (CH) rats. Elevated blood glucose was observed during intraperitoneal
glucose tolerance test in HFD-fed rats over CH-fed rats. Insulin tolerance test
(ITT) was unremarkable among the three groups. Gavage of ENSURE resulted in high
glucagon-like peptide 1 (GLP-1) release from SCI rats over naïve controls. An
elevation in terminal total GLP-1 was measured, with a marked reduction in
circulating dipeptidyl peptidase 4, the GLP-1 cleaving enzyme, in SCI rats,
compared with naïve. Increased glucagon mRNA in the pancreas and reduced
immunoreactive glucagon-positive staining in the pancreas in SCI rats compared
with controls suggested increased glucagon turnover. Finally, GLP-1 receptor
gene expression in the ileum, the primary source of GLP-1 production and
release, in SCI rats suggests the responsivity of the gut to altered circulating
GLP-1 in the body. In conclusion, the actions of GLP-1 and its preprohormone,
glucagon, are markedly uncoupled from their actions on glucose control in the
SCI rat. More work is required to understand GLP-1 in the human.


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