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Part 5

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waveurflag's version from 2018-03-29 02:38

Section

Question Answer
glycogenolysisLiver supplies glucose by turning glycogen→ glucose
gluconeogenesisThe liver also can manufacture necessary sugars or glucose by harvesting amino acids, waste products and fat byproducts
• Islets of Langerhans in pancreasOrgan Responsible for Glucose Metabolism
• A C-peptide test is done to:o Help tell the difference between type 1 diabetes and type 2 diabetes. (know below image) o With HIGH BLOOD GLUCOSE, tell between extremely low C-peptide, high C-peptide, and low C-peptide
C peptide is removed by our kidneys and stays in our system ~6 times longer than insulin (which is removed by the liver)
Type 2 Diabetes• High levels of glucose causes insulin resistance and destruction of beta cells (that produce insulin), high c-peptide is a sign of it
GLUT 4 Transporter• Transporter on target cells that need glucose • Responsible for uptake of glucose into target cell • Glucose enters with sodium • Na K ATPase drives gradient of sodium to drive gradient of Na-glucose symporter (secondary active transport)
How does insulin allow glucose to enter into cells?• GLUT 4 must be at the membrane
HOW DOES THE GLUT4 TRANSPORTER GET TO THE MEMBRANE??• Tyrosine kinase pathway – linked to diabetes! • GLUT transporter stays at membrane through tyrosine kinase • If GLUT is at the incorrect spot, cannot help glucose get into cell
• Insulin receptor substrate (IRS) 1tyrosine kinase phosphorylates this o Docking protein
• MAP kinase activated by IRS o Helps phosphorylate GLUT 4 to the membrane
Treatments for Types of Diabetes: Type 1give back insulin
Treatments for Types of Diabetes: Type 2– help pancreas be more efficient at producing insulin, or help GLUT4 to uptake more effieicnetly
RAPID ACTING Insulin Aspart (Novolog)• A single amino acid has been slightly changed in its molecular structure. • Has a peak soon after administration • This change helps the fast-acting insulin analog be absorbed quickly into the bloodstream. As a result, it starts working in minutes, which allows one to take insulin and eat right away. • Fast-acting insulin analogs are considered to act similarly to the way insulin is released in people without diabetes mellitus. ALLOWS MORE CONTROL WHEN EATING SCHEDULES ARE NOT REGULAR Insulin Aspart Sequence • No c-peptide! • Original sequence – proline o Asp has a negative charge for increased charge repulsing. Faster acting insulin
RAPID ACTING Insulin Lispro (Humalog)• Engineered through recombinant DNA technology, the lysine and proline residues on the C-terminal end of the B-chain are reversed. • This modification does not alter receptor binding, • but blocks the formation of insulin dimers and hexamers. • This allows larger amounts of active monomeric insulin to be immediately available for postprandial injections. • Insulin Lispro sequence o Switching order, now they are repulsing each other o “Flipping magnets” o Lysine is positively charged o Positively charged driven repulsion
Detemir LONG ACTING is unique in the sense that a C14 fatty acid has been covalently bonded to lysine in position B29 and the terminal threonine of human insulin in position B30 has been removed.
• Albumin binding contributes almost as much to the prolongation of action of insulin detemir, as does the di-hexameric self-association.
LONG ACTING Insulin Glargine (Lantus)• pH and solubility important in insulin glargine Insulin Glargine Sequence • Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain.
• When a long acting and a bolus insulin are given together to a patient?• To maintain steady levels of insulin between meals
• Which patient needs sulfonylureas?Those with failing beta cells that produce sub-optimal amounts of insulin
SULFONYLUREAS• Sulfonylureas bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells. • This inhibits a tonic, hyperpolarizing efflux of potassium, thus causing the electric potential over the membrane to become more positive.• This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.
Dipeptidyl Peptidase IV (DPP-IV) Inhibitors• GLP-1 will stimulate insulin release and inhibit glucagon release • GLP-1 IS GOOD AND HEALTHY!
• HEALTHY PATIENT:• ↓ DPP4, ↑ GLP-1, ↑ INSULIN
• DIABETIC PATIENTS:• ↑DPP4, ↓GLP-1, ↓INSULIN
Sitagliptin• Is a DPP-IV Inhibitors • Diabetes Type 2 • Oral tablets • WARNING: A 2013 study of the DPP-4 inhibitor sitagliptin reported found "worrisome changes in the pancreases of the rats that could lead to pancreatic cancer".
Thiazolidinedione PPAR AGONISTS• Thiazolidinediones (TZDs) are potent insulin sensitizers that act through the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) • Are highly effective oral medications for type 2 diabetes. Direct action of PPAR-γ activation on the genes involved in glucose homeostasis is not well understood.
Biguanide (Metformin)• The main use for metformin is in the treatment of diabetes mellitus type 2, especially in overweight people. o Main side effect is weight loss! Effects of Metformin Side Effects • Upset stomach • Metformin has also been reported to decrease the blood levels of thyroid-stimulating hormone in people with hypothyroidism  unsure why
MOA Metformindecreases hyperglycemia primarily by suppressing glucose production by the liver (hepatic gluconeogenesis). The "average" person with type 2 diabetes has three times the normal rate of gluconeogenesis; metformin treatment reduces this by over one-third
Metformin can be anticancer
Alpha Glucosidase Inhibitors• Acarbose inhibits ENZYMES needed to digest carbohydrates, specifically, alpha-glucosidase enzymes in the brush border of the small intestines and pancreatic alpha-amylase. • Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules.
Prednisolone/Dexamethasone (anti-inflammatory)• Given for severe asthma, organ transplantation, cystic fibrosis, inflamatory bowel disease • CAN CAUSE STEROID-INDUCED DIABETES!!!! • Steroid drugs are linked to steroid-induced diabetes because of its increased binding to glucocorticoid receptors
• PREDNISONE raises raises the level of glucose in the blood by stimulating the liver to produce glucose from stored non-carbohydrate sources such as proteins and lipids and to release it into the blood (gluconeogenesis)
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