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endoplasmic reticulum in the brain (Oleinik et al., 2023

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doi:10.1016/s1357-2725(97)00128-3 Carow, Berit, and Martin E Rottenberg

10% excreted unchanged by the kidney hepatic dysfunction Glimepiride: (Amaryl) monotherapy -- once a day administration or in combination with insulin most potent -- lowest dose of the sulfonylureas long duration of action: half-life = 5 hours hepatic metabolism: complete to inactive products Secondary Failure and Tachyphylaxis to Sulfonylureas: Treatment failures occur Possibly due to pancreatic B cell refractoriness or to loss of dietary compliance Combination of sulfonylureas and insulin would appear justified only in the presence of severe insulin resistance Biguanides Metformin: (Glucophage) Proposed Mechanism of Action: glycolysis stimulation-- increased glucose removal from blood decreased hepatic gluconeogenesis decreased glucose absorption rate from the GI tract reduced plasma glucagon in patients with refractory obesity and insulin resistance Advantages: does not cause hypoglycemia does not increased weight May be used in combination with sulfonylureas when sulfonylurea monotherapy is not effective Toxic/adverse effects: most common -- gastrointestinal (20% frequency) anorexia, nausea, vomiting, diarrhea dose-related usually occurs upon initiation of therapy -- often transient in effect Decreased vitamin B12 absorption

Watanabe et al., 2020)

Here, we demonstrated that OxLDL also promotes chronic mitochondrial dysfunction, which was prevented in macrophages overexpressing either mitochondrial or cytosolic GR