Biochemistry of Insulin Variants

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Questions and Answers

What method is primarily used to administer glucagon during hypoglycemic emergencies?

Intramuscular route (correct)

Oral route

Subcutaneous route

Intravenous route

What is a significant limitation of glucagon when hepatic glycogen stores are depleted?

It cannot be administered intramuscularly

It causes renal toxicity

It leads to severe gastrointestinal distress

Its hyperglycemic action is transient (correct)

What is a common side effect associated with glucagon use?

Dizziness

Nausea and vomiting (correct)

Hypotension

Diarrhea

What mechanism underlies the hyperglycemic effect of diazoxide?

Inhibition of insulin secretion Signup and view all the answers

Which of the following properties does glucagon share with diazoxide?

Both have hyperglycemic actions Signup and view all the answers

Which channel does diazoxide interact with to exert its effects?

KATP channel Signup and view all the answers

What is the primary mechanism of action of metformin in the liver?

Suppression of gluconeogenesis Signup and view all the answers

Which of the following effects is NOT associated with the activation of AMPK?

Enhanced lipogenesis Signup and view all the answers

What is a common side effect of thiazolidinediones?

Fluid retention Signup and view all the answers

What is the primary action of α-glucosidase inhibitors in the intestinal tract?

Reduce intestinal absorption of carbohydrates Signup and view all the answers

Which process is NOT facilitated by the binding of thiazolidinediones to PPARγ?

Decreased fatty acid uptake Signup and view all the answers

Which statement regarding metformin's pharmacokinetics is true?

It is excreted unchanged in the urine. Signup and view all the answers

Which of the following is a common side effect of α-glucosidase inhibitors?

Flatulence Signup and view all the answers

The primary effect of activated AMPK includes all of the following EXCEPT:

Stimulation of gluconeogenesis Signup and view all the answers

What mechanism do gliflozins utilize to lower blood glucose levels?

Inhibit sodium glucose co-transporter (SGLT-2) Signup and view all the answers

What is a notable pharmacokinetic characteristic of acarbose?

Minimal absorption with renal clearance Signup and view all the answers

How do thiazolidinediones primarily affect glucose metabolism?

They enhance the effectiveness of insulin, increasing glucose uptake. Signup and view all the answers

Which patient demographic is particularly at higher risk for urinary tract infections due to gliflozin use?

Postmenopausal women Signup and view all the answers

The transport of metformin into cells is primarily mediated through which of the following?

Organic cation transporters Signup and view all the answers

What type of reaction can occur with acarbose regarding hepatic transaminases?

Mild and symptomatic elevations Signup and view all the answers

Which of the following correctly describes the administration method of liraglutide?

Subcutaneous injection once daily Signup and view all the answers

Which of the following statements about exenatide is true?

It is administered via a pen device. Signup and view all the answers

Which alteration in the amino acid sequence of insulin results in increased stability and solubility?

Reversing proline and lysine Signup and view all the answers

What is the primary mechanism by which glucose stimulates insulin secretion?

Inhibition of ATP-sensitive potassium channels Signup and view all the answers

Which of the following combinations represents a mixed insulin formulation?

NPH and regular insulin 70:30 Signup and view all the answers

Which of the following is NOT a common side effect of insulin therapy?

Dehydration Signup and view all the answers

What distinguishes the first generation sulphonylureas from the second generation?

Second generation are more potent and have fewer side effects Signup and view all the answers

Which insulin formulation is characterized by prolonged action and a predictable kinetic profile?

Insulin glargine Signup and view all the answers

Which glucose transporter is activated by the binding of insulin to its receptor?

GLUT-4 Signup and view all the answers

What effect does insulin have that contributes to weight gain?

Promotion of protein synthesis Signup and view all the answers

What is a significant side effect of Thiazolidinediones that could exacerbate a specific cardiovascular condition?

Fluid retention Signup and view all the answers

Which statement best describes the metabolism of Thiazolidinediones?

They undergo metabolism by liver enzymes. Signup and view all the answers

What effect does co-administration of rifampin have on Thiazolidinediones?

It induces liver enzymes and decreases plasma concentrations. Signup and view all the answers

What is the primary action of Dipeptidyl peptidase-4 (DPP-4) inhibitors like sitagliptin?

Potentiate endogenous incretins GLP-1 and GIP. Signup and view all the answers

Which of the following statements about GLP-1 agonists is TRUE?

Exenatide requires subcutaneous injections before meals. Signup and view all the answers

What is the primary pharmacokinetic characteristic of Gliptins?

They are absorbed from the small intestine and excreted unchanged in urine. Signup and view all the answers

Which of the following is NOT a reported side effect of Gliptins?

Weight gain Signup and view all the answers

Which group of patients should avoid the use of Thiazolidinediones?

Patients with heart failure Signup and view all the answers

Study Notes

Insulin Variants and Mechanisms

Alterations in human insulin's amino acid sequence enhance stability and modify action duration, such as insulin lispro from reversing proline and lysine.
Mixed insulin formulations include 70:30 combinations of NPH and regular insulin, as well as lispro protamine/lispro in ratios of 50/50 and 75/25.
Insulin glargine offers prolonged effects with a predictable kinetic profile.

Insulin Secretion Regulation

Glucose serves as the primary insulin secretagogue.
ATP-sensitive potassium channels contribute to membrane depolarization, initiating insulin release from storage vesicles.
Insulin binds to enzyme-linked transmembrane receptors, activating glucose transport processes via Glut-4 in adipose and muscle tissues.

Insulin Side Effects

Common side effects include hypoglycemia, weight gain, allergic reactions, injection site reactions, lipoatrophy, and lipohypertrophy.

Oral Hypoglycemic Agents

Sulphonylureas

Substituted arylsulphonylureas, divided into first-generation (e.g., tolbutamide, chlorpropamide) rarely used due to severe hypoglycemia risk.
Second-generation includes glibenclamide, gliclazide, glipizide, and glimepiride, with less severe hypoglycemic effects.

Metformin

Acts primarily by suppressing hepatic gluconeogenesis and is best absorbed in the small intestine; does not bind plasma proteins.
Common side effects include gastrointestinal disturbances (anorexia, diarrhea, nausea) and lactic acidosis, with a rare incidence of hypoglycemia.

Thiazolidinediones (Glitazones)

Rosiglitazone and pioglitazone bind to PPARγ in adipose tissue, enhancing glucose and fatty acid uptake but contributing to weight gain.
Slow onset of blood glucose-lowering effects, with significant side effects including weight gain and fluid retention, potentially exacerbating heart failure.

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors (Gliptins)

Inhibit DPP-4 enzyme, enhancing bioavailability of incretins like GLP-1 and GIP to lower blood glucose levels.
Common side effects include nausea, stomach pain, and flu-like symptoms.

GLP-1 Agonists

These agents activate GLP-1 receptors, stimulating insulin biosynthesis and release.
Administered via subcutaneous injections, with side effects including nausea, vomiting, and delayed gastric emptying.

α-Glucosidase Inhibitors

Inhibit α-glucosidase in the intestine, reducing starch and disaccharide absorption, resulting in decreased postprandial plasma glucose.
Examples include acarbose and miglitol, with common gastrointestinal side effects such as flatulence and diarrhea.

SGLT-2 Inhibitors (Gliflozins)

Agents like dapagliflozin and canagliflozin block sodium-glucose co-transport in kidneys, reducing glucose absorption and blood glucose levels.
Short half-life and plasma protein binding; they increase urinary tract infection risk.

Glucagon and Diazoxide for Hypoglycemia

Glucagon, produced via recombinant DNA, treats severe hypoglycemia, administered intravenously, intramuscularly, or subcutaneously.
Diazoxide, an oral vasodilator with hyperglycemic effects, prevents insulin secretion through KATP channel interaction.

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Description

This quiz explores the structural modifications of human insulin, including its amino acid sequence and protein structure alterations. Learn about various insulin types such as insulin lispro, NPH, and glargine, and their effects on solubility and action duration.