Altered chronic glycemic control in a clinically relevant model of rat thoracic spinal contusion

Abstract

The lifetime risk for Type-2 diabetes mellitus remains higher in people with spinal cord injuries than in the able-bodied population. However, the mechanisms driving this disparity remain poorly understood. The goal of the current 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 CH rats. Elevated blood glucose was observed during intraperitoneal GTT in HFD-fed rats over CH-fed rats. ITT was unremarkable amongst the three groups. Gavage of ENSURE resulted in high 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 (DPP4), the GLP-1 cleaving enzyme, in SCI rats, compared to naïve. Increased glucagon mRNA in the pancreas and reduced immunoreactive glucagon-positive staining in the pancreas in SCI rats compared to 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.

Plasticity of colonic enteric nervous system following spinal cord injury in male and female rats

“…However, this mechanism was only demonstrated through the use of isolated ICC‐lineage cells and organotypic cultures exposed to hyperglycemia. Our in vivo model of SCI does not induce long‐term hyperglycemia in rats fed a standard laboratory diet but only when fed a high fat diet 56,57 . Furthermore, only the responsiveness to a cholinergic agonist was explored and cell counts for cholinergic excitatory and nitrergic inhibitory enteric neurons were not performed nor were evoked responses in the form of smooth muscle junction potentials.…”

“…Our in vivo model of SCI does not induce long-term hyperglycemia in rats fed a standard laboratory diet but only when fed a high fat diet. 56,57 Furthermore, only the responsiveness to a cholinergic agonist was explored and cell counts for cholinergic excitatory and nitrergic inhibitory enteric neurons were not performed nor were evoked responses in the form of smooth muscle junction potentials. Our previous report of reduced cholinergic and nitrergic myenteric neuron populations in SCI rats would be consistent with a loss-of-function, despite the increase in ICC networks.…”