Glucose Metabolism - M3 and SR1 activation may restore blood pressure to normal levels as I posted yesterday. Abnormal blood pressure resulting in impaired cerebral blood flow is associated with AD. M3 also plays a role in glucose metabolism. Impaired glucose metabolism is a dementia/AD risk.
New findings on glucose metabolism, oxidative stress and Alzheimer’s disease May 22, 2017 “Glucose metabolism, oxidative stress and AD
Impairment in glucose metabolism and insulin resistance has been a hot topic in AD research in recent years, and for good reason. Type II diabetes is a known risk factor for AD – in a recent review, Saedi and colleagues noted a 45–90% association of diabetes with AD, and also that even pre-diabetes, regardless of progression, confers a higher risk of AD. Brain atrophy has also been noted in diabetic patients (3).
The link between Type II diabetes and AD may lie in the effects of glucose metabolism dysregulation and oxidative stress. Verdile et al. note that 3 aspects of insulin resistance present in Type II diabetes, hyperglycemia, hyperlipidemia and hyperinsulinemia, are all known to boost accumulation of amyloid beta, one of the hallmarks of Alzheimer’s disease, and that the inverse, amyloid beta promoting insulin resistance, has also been demonstrated in the liver. Even independent of insulin resistance, studies have shown that excess glucose leads to persistently higher amyloid beta in interstitial fluid as well as lowered neuronal activity and hippocampal metabolism, suggesting that these damaging processes may begin even prior to full-blown T2D (4).”
Role of the M3 muscarinic acetylcholine receptor in ß-cell function and glucose homeostasis
Abstract
The release of insufficient amounts of insulin in the presence of elevated blood glucose levels is one of the key features of type 2 diabetes. Various lines of evidence indicate that acetylcholine (ACh), the major neurotransmitter of the parasympathetic nervous system, can enhance glucose-stimulated insulin secretion from pancreatic ß-cells. Studies with isolated islets prepared from whole body M3 muscarinic ACh receptor knockout mice showed that cholinergic amplification of glucose-dependent insulin secretion is exclusively mediated by the M3 muscarinic receptor subtype. To investigate the physiological relevance of this muscarinic pathway, we used Cre/loxP technology to generate mutant mice that lack M3 receptors only in pancreatic ß-cells. These mutant mice displayed impaired glucose tolerance and significantly reduced insulin secretion. In contrast, transgenic mice overexpressing M3 receptors in pancreatic ß-cells showed a pronounced increase in glucose tolerance and insulin secretion and were resistant to diet-induced glucose intolerance and hyperglycaemia. These findings indicate that ß-cell M3 muscarinic receptors are essential for maintaining proper insulin secretion and glucose homeostasis. Moreover, our data suggest that enhancing signalling through ß-cell M3 muscarinic receptors may represent a new avenue in the treatment of glucose intolerance and type 2 diabetes.
Market Data 
Markets 
AI
