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A&P Lecture 11

QuestionAnswer
Incretins are metabolic hormones released from the gut after eating
Examples of incretins include Glucagon-like peptide (GLP-1) Gastric inhibitory polypeptide (GIP)
What cell produces Incretins? Enteroendocrine cells (specifically L-cells for GLP-1) in the small intestine + colon secrete these hormones
Stimulus for incretin release Macromolecules- primarily carbohydrates, lipids, and proteins + gastric distension
Targets and effects for incretins Pancreas increase insulin and decrease glucagon secretion
Targets and effects for incretins Gastrointestinal tract decrease gastric emptying (this increases nutrient absorption)
Targets and effects for incretins Brain (spec- hypothalamus) reduces appetite and increases satiety (feeling full)
Incretins prepare the body for incoming nutrients by coordinating insulin release, sowing digestion, and reducing appetite
GLP-1 has a very WHAT life span short! 1-2 mins
Why is GLP-1 life span so short? GLP 1 is rapidly broken down by the enzyme DPP-4 (dipeptidyl peptidase-4) DDP-4 is widely expressed by cells and can be soluble or membrane bound
The gila monster The gila monster has a unique life style Eats infrequently (sometimes only a few times a year) Must store and regulate nutrients efficiently
Reptile venom and saliva are rich in Peptides Enzymes Signaling molecules PES
These compounds (PES) often Act on specific receptors Have strong physiological effects
Exdenin-4 Was discovered in the 1990s in the saliva of the gila monster It mimics human GLP-1 but is resistant to rapid breakdown (DPP-4), giving it a much longer lifespan *This discovery led to GLP-1 receptor agonist drugs used to treat diabetes and obesity*
Most GLP-1 receptors agonists end with what? Which refers to what? -glutide, this refers to the fact these drugs are proteins that mimics glucose-like peptide
These drugs are modified versions of endogenous GLP-1 that are resistant to DPP-4 breakdown, allowing them to last longer in the body
First GLP-1 RA: Exenatide (byetta) FDA approved in 2005 Derived from extendin-4 (the gila monster saliva) Initially used to treat type 2 diabetes
Goals of GLP-1 RA Exenatide (byetta) Improved blood glucose control Lower risk of hypoglycemia compared to insulin Insulin carries the risk of lowering blood glucose to dangerous levels
Results of GLP-1 RA Exenatide (byetta) Patients were found to exhibit reduced blood glucose levels!! Weight loss- patients lost 15% of their body compared to 2% in placebo controls
Why does this matter? Improved body weight regulation - Reduces insulin resistance, inflammation, and metabolic stress - Lower risk of cardiovascular and fatty liver disease - Improves mobility, energy, and metabolic health
Improved glycemic control Lower HbA1c = better long-term blood glucose control Reduced risk of: - Neuropathy - Retinopathy - Kidney disease
Results of the GLP-1 RA Decreased complications Increase quality of life Increase life expectancy
Why GLP-1 RA are a public health game changer GLP-1 drugs target two of the most common and costly diseases in the U.S: obesity and type 2 diabetes As of 2022-2023, approximately 42% of U.S adults are obese 1 in 8 Americans are living with diabetes (95% are type 2)
These two disorders are estimated to cost the US over 2 trillion a year So yeah. curing diabetes is a good thing
Beneficial findings Clinically significant weight loss (10-20% body weight in many patients0 ~20% reduction in risk of major adverse cardiovascular events High risk patients ~19% decrease in end stage kidney disease
Small study- slightly reduced risk of blood cancer Reduced insulin resistance Reduced blood glucose levels
A meta analysis statistical method that combines data from multiple independent studies addressing the same research question
Side effects of GLP-1s Most common = GI issues (nausea, diarrhea, vomiting) Common = reduced bone density, increased risk for fracture Common = mouscle loss (as high as ⅓ of weight loss is muscle) Rare but severe = pancreatitis, gall stones, thyroid tumors
Limitations: Many positive effects are lost when stopping GLP1s (weight and CV protection) Expensive, not always covered by insurance Unknown long-term consequences
Future directions Combination treatment- to improve efficacy and reduce side effects Improve dosage with expanded use Improving understanding of side effects Reducing costs and improving access
Created by: liladdoyle
 

 



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