Blood-Brain Glucose Transfer in Alzheimer’s disease: Effect of GLP-1 Analog Treatment

Abstract

There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer’s disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMRglc) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMRglc in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD to treatment with liraglutide (n = 18) or placebo (n = 20) for 6 months, and determined the blood-brain glucose transfer capacity (T max) in the two groups and a healthy age matched control group (n = 6). In both AD groups at baseline, T max estimates correlated inversely with the duration of AD, as did the estimates of CMRglc that in turn were positively correlated with cognition. The GLP-1 analog treatment, compared to placebo, highly significantly raised the T max estimates of cerebral cortex from 0.72 to 1.1 umol/g/min, equal to T max estimates in healthy volunteers. The result is consistent with the claim that GLP-1 analog treatment restores glucose transport at the BBB.

Weight loss more than glycemic control may improve testosterone in obese type 2 diabetes mellitus men with hypogonadism

“…However, in a hypogonadal perspective, together with improving glycemic control, both SGLT2i and GLP-1RA have shown an anti-inflammatory effect at different levels, even in the brain, possibly mitigating the negative effects of lowgrade inflammation of the hypothalamus. [37][38][39] Then, higher TT levels reaching the normal range could reduce insulin resistance and help improving metabolic parameters, as confirmed by two well-designed randomized controlled clinical studies carried out in healthy adult men. 10,40,41 It is worth noting that a higher reduction in body weight was found in the present study compared to data available in the literature from cardiovascular outcome trials.…”

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

“…Liraglutide has shown its unique neuroprotective effect in reducing the level of oxidative stress, apoptosis, and inflammation as well as in promoting the proliferation of neurons and the recovery of cognitive function in the central nervous system in experimental models and clinical patients (Zhu et al, 2016;Gejl et al, 2017;Guthrie, 2018). Moreover, liraglutide exerts positive effects on weight loss, blood pressure, hyperlipidemia, and glycemic control in the clinic.…”

Clinical Evidence of Antidepressant Effects of Insulin and Anti-Hyperglycemic Agents and Implications for the Pathophysiology of Depression—A Literature Review

“…GLP-1, as well as its analogues, can readily cross the BBB and exert various physiological effects [189]. GLP-1 is also able to facilitate glucose transport across the BBB, which is crucial in the homeostasis of brain metabolism [190]. Additionally, growing evidence shows that GLP-1 modulates inflammation and has neuroprotective and neurotrophic effects whose relationship to the pathophysiology of depression is widely accepted [191][192][193].…”