Select the class of Anti-diabetic medication that works in the specified organ to prevent hyperglycemi a. Select all that applies. Brain (E)

Glucagon-like peptide-1 (GLP-1) receptor agonists exert their effects through multiple mechanisms, one of which is centrally mediated in the brain. These agents activate GLP-1 receptors in the hypothalamus, which plays a crucial role in regulating appetite. This activation enhances satiety and reduces food intake, leading to weight loss and subsequent improvement in glycemic control. This central nervous system action is a key component of their therapeutic effect in managing type 2 diabetes and preventing hyperglycemia, distinguishing them from other classes that act primarily on peripheral organs like the pancreas, liver, or kidneys.

A. Sulfonylureas: These agents primarily act on the pancreatic beta-cells to stimulate the secretion of insulin.

B. Alpha-Glucosidase Inhibitors: Their mechanism is localized to the brush border of the small intestine, where they delay carbohydrate absorption.

C. DPP4 Inhibitors: These drugs increase endogenous GLP-1 levels, but their primary action is inhibiting the DPP-4 enzyme, which is widespread, not specifically targeting the brain.

E. Thiazolidinediones: These act as PPAR-γ agonists, primarily increasing insulin sensitivity in adipose tissue, skeletal muscle, and the liver.

F. Biguanide: Metformin's primary effect is decreasing hepatic glucose production and improving peripheral insulin sensitivity.

G. SGLT2 inhibitors: These drugs work in the proximal tubules of the kidneys to inhibit glucose reabsorption, thereby increasing urinary glucose excretion.

1. Drucker

D. J. (2018). Mechanisms of Action and Therapeutic Application of Glucagon-Like Peptide-1. Cell Metabolism

27(4)

740–756. (See section "GLP-1 Receptor Signalling in the Central Nervous System

" p. 747

discussing appetite suppression and neuroprotection). https://doi.org/10.1016/j.cmet.2018.03.001

2. Brunton

L. L.

Dandan

R. H.

& Knollmann

B. C. (Eds.). (2018). Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. (In Chapter 47

"Endocrine Pancreas and Pharmacotherapy of Diabetes Mellitus and Hypoglycemia

" the section on Incretin-Related Drugs describes GLP-1 receptor agonists acting on the CNS to suppress appetite).

3. University of California

San Francisco (UCSF) Diabetes Teaching Center. (n.d.). Pharmacologic Management of Type 2 Diabetes. UCSF School of Medicine. (The module on GLP-1 Receptor Agonists details their mechanism of action

including slowing gastric emptying and acting on the brain to control appetite). Retrieved from https://dtc.ucsf.edu/types-of-diabetes/type2/treatment-of-type-2-diabetes/medications-and-therapies/type-2-non-insulin-therapies/pharmacologic-management-of-type-2-diabetes/