Key result
In a rat model of spinal cord injury, high-fat diet consumption induced weight gain and elevated blood glucose, with marked uncoupling of GLP-1 and glucagon actions on glucose control.
Why the study?
The lifetime risk for Type 2 diabetes mellitus is elevated in people with spinal cord injuries, but the mechanisms driving this disparity remain poorly understood.
Does a high-fat diet alter glycemic regulation in a rodent model of spinal cord injury?
Does a high-fat diet alter glycemic regulation in a rodent model of spinal cord injury?
In a rat model of spinal cord injury, the actions of GLP-1 and its preprohormone, glucagon, are markedly uncoupled from their actions on glucose control.
Uncoupled GLP-1 and glucagon signaling from glucose control in SCI rats cautions against direct translation of incretin therapies; leaves open mechanisms of elevated diabetes risk for human studies.
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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Harris et al. (2022) studied Spinal cord injury. High-fat diet vs. Chow diet was evaluated on Glycemic regulation (tolerance to glucose, insulin, and ENSURE mixed meal). In a rat model of spinal cord injury, high-fat diet consumption induced weight gain and elevated blood glucose, with marked uncoupling of GLP-1 and glucagon actions on glucose control.
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