Purpose: Brain insulin resistance is related to both diabetes and Alzheimer's disease. We investigated whether both chungkookjangs, soybeans fermented in a traditional method (TFC) and with Bacillus lichenifomis (SFC), can protect against cognitive dysfunction and glucose dysregulation in rats with Alzheimer's disease and type 2 diabetes.
Methods: Partial pancreatectomy (Px) and ICV β-amyloid (25-35) infusion into the CA1 region were fed either control diet (AD-CON), 10% cooked soybeans (CSB), 10% TFC, or 10% SFC in a high fat diet for 8 weeks. Px rats infused β-amyloid (35-25) as a normal-control group (Non-AD-CON).
Results: SFC increased isoflavonoid aglycones, DDMP soyasaponin βg, E soyasaponin Be and lysoposphatidylcholines in comparison to CSB. SFC markedly decreased its accumulation in β-amyloid deposition in AD rats and improved hippocampal insulin signaling (pAkt → pGSK → pTau) that exacerbated in AD-CON rats. AD rats markedly impaired cognitive function than Non-AD-CON rats as measured by a water maze and passive avoidance tests while the disturbance was prevented in an ascending order of CON < CSB and TFC < SFC. In comparison to Non-AD rats, AD-CON rats lowered whole body glucose infusion rates and increased hepatic glucose output at hyperinsulinemic state during euglycemic hyperinsulinemic clamp which SFC normalized in AD rats. Interestingly, insulin secretion, especially at the second phase during hyperglycemic clamp, was higher in AD-CON rats, compared to Non-AD rats while CSB, TFC, SFC lowered it in AD-rats. However, SFC restored β-cell mass in AD rats that reduced β-cell mass by increased β-cell apoptosis.
Conclusions: β-Amyloid accumulation in the hippocampus exacerbated insulin resistance and decreased β-cell mass and SFC prevented their exacerbation in AD diabetic rats.