Diabetes Medication Mechanisms Quiz

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Questions and Answers

What is the primary mechanism by which sitagliptin and similar drugs enhance insulin release?

Promotion of gastric emptying

Inhibition of glucagon production

Direct stimulation of beta cells

Enhancement of glucose-dependent insulin release (correct)

Which of the following is an effect of GLP-1 agonists?

Increase in hepatic glucose production

Appetite suppression (correct)

Decrease in insulin sensitivity

Weight gain

Which of these is a common side effect associated with GLIFLOZINS?

Insulin resistance

Headache

Diabetic ketoacidosis (correct)

Upper respiratory tract infection

What is a distinguishing feature of the GLP-1 agonist tirzepatide?

It mimics both GLP-1 and GIP Signup and view all the answers

Which drug class is primarily used to prevent reabsorption of glucose in the kidneys?

SGLT-2 inhibitors Signup and view all the answers

Which class of medications primarily stimulates insulin secretion in a glucose-independent manner?

Insulin secretagogues Signup and view all the answers

What is a common side effect associated with sulfonylureas?

Hypoglycemia Signup and view all the answers

Which of the following insulin preparations is classified as intermediate-acting?

NPH Signup and view all the answers

Which medication is categorized as a DPP-4 inhibitor?

Sitagliptin Signup and view all the answers

Which insulin is specifically designed for prandial bolus use?

Regular (unmodified insulin) Signup and view all the answers

What role do beta cells play in the pancreatic islets?

They produce insulin and amylin. Signup and view all the answers

Which of the following accurately describes the organization of pancreatic exocrine and endocrine cells?

Endocrine cells secrete hormones near capillaries. Signup and view all the answers

Which hormone is secreted by the pancreas when blood glucose levels are low?

Glucagon Signup and view all the answers

Which of the following pairs represents the primary targets for insulin action?

Liver, skeletal muscle, and adipose tissue. Signup and view all the answers

How long does insulin typically remain in circulation before it is destroyed by the liver and kidney?

Approximately 6 minutes. Signup and view all the answers

What effect do incretin hormones like GLP-1 and GIP have on insulin release?

They increase prandial insulin release. Signup and view all the answers

Which type of cell in the pancreatic islets is responsible for producing glucagon?

Alpha cells Signup and view all the answers

What is one of the main functions of somatostatin produced by delta cells?

Inhibits glucagon release. Signup and view all the answers

Which of the following symptoms is specifically associated with uncontrolled Type 1 diabetes mellitus?

Rapid weight loss Signup and view all the answers

What is the recommended HbA1c cut-off point for diagnosing diabetes?

48 mmol/mol (6.5%) Signup and view all the answers

Which of the following is a major cause of Type 2 diabetes mellitus?

Defective insulin release Signup and view all the answers

The term 'mellitus', used to describe diabetes, means what?

Sweet like honey Signup and view all the answers

During which age period is Type 1 diabetes mellitus most commonly diagnosed?

Under 30 years Signup and view all the answers

What is the main reason for polyuria in diabetes mellitus?

Excess glucose in the blood Signup and view all the answers

Which glucose concentration measurement indicates diabetes when conducted during a random venous plasma test?

≥ 11.1 mM Signup and view all the answers

Which of the following is NOT a sign or symptom of diabetes mellitus?

High blood pressure Signup and view all the answers

What is the primary action of metformin?

Inhibiting glucose absorption from the gut Signup and view all the answers

Which of the following correctly describes the side effect profile of thiazolidinediones (TZDs)?

Low risk of hypoglycaemia and potential for weight gain Signup and view all the answers

Which statement about repaglinide is true?

It has a lower risk of hypoglycaemia compared to sulphonylureas. Signup and view all the answers

What is the mechanism of action of starch blockers like acarbose?

Inhibits α-glucosidase enzymes in the gut Signup and view all the answers

What is a commonly reported gastrointestinal side effect of biguanides?

Lactic acidosis Signup and view all the answers

Which benefit is associated with using gliptins?

Enhancement of incretin levels Signup and view all the answers

Which characteristic correctly describes the action of thiazolidinediones on insulin sensitivity?

They primarily act to reduce peripheral insulin resistance. Signup and view all the answers

What is the primary adverse effect linked to starch blockers?

GI upset Signup and view all the answers

What is the primary function of glucagon in the body?

Increases energy release during fasting Signup and view all the answers

What is the role of insulin in the regulation of blood glucose levels?

Stimulates glucose uptake in insulin-sensitive tissues Signup and view all the answers

Which of the following describes the synthesis process of insulin?

Insulin is cleaved from proinsulin in vesicles of the Golgi apparatus Signup and view all the answers

What common feature do insulin and glucagon share in their regulation?

Both use negative feedback mechanisms for their secretion Signup and view all the answers

What differentiates Type 1 diabetes from Type 2 diabetes?

Type 1 diabetes results from the destruction of beta cells in the pancreas Signup and view all the answers

What is the half-life of amylin in circulation compared to glucagon?

Amylin has a shorter half-life than glucagon Signup and view all the answers

Which of the following statements about insulin and glucagon is false?

Both insulin and glucagon are released in response to low blood glucose Signup and view all the answers

Which transporters primarily facilitate glucose uptake in insulin-sensitive tissues?

GLUT4 transporters Signup and view all the answers

Study Notes

Endocrine Pancreas, Diabetes Mellitus & Pharmacotherapeutics

The pancreas is a flattened organ located posterior and slightly inferior to the stomach.
It functions as both an endocrine and exocrine gland.
Histologically, it consists of pancreatic islets (Islets of Langerhans) and acini (enzyme-producing exocrine cells).
The pancreas is approximately 5 inches long and has a head, body, and tail.
Endocrine cells within pancreatic islets produce hormones.
Exocrine acinar cells surround a small duct.
Endocrine cells (e.g alpha, beta, delta, F cells) secrete hormones near a capillary.
Approximately 1 to 2 million pancreatic islets are present per human pancreas (making up 1-2% of its weight).
The pancreas contains four types of endocrine cells.

Cell Types in Pancreatic Islets

Alpha cells (20%): produce glucagon.
Beta cells (70%): produce insulin and amylin.
Delta cells (5%): produce somatostatin.
PP cells: produce pancreatic polypeptide.
The human pancreas contains 8 mg of insulin and secretes 0.5 to 1 mg daily.
Insulin is rapidly destroyed by the liver and kidneys (t½ in circulation: ~6 minutes).

Regulation of Blood Glucose

When blood glucose increases, the pancreas secretes insulin to lower blood glucose levels.
Glucose enters beta cells via GLUT2 transporters.
ATP production increases.
ATP-sensitive potassium (KATP) channels close.
Insulin is released.
Insulin reduces blood glucose.
When blood glucose is low, the pancreas secretes glucagon to maintain constant blood glucose levels.
Glucagon increases blood glucose.
Insulin and glucagon have opposing actions.

Primary Targets for Insulin Action

Liver
Skeletal muscle
Adipose tissue
Pancreatic alpha cells (to inhibit glucagon release)
Skeletal muscle and fat cells are dependent on insulin for glucose uptake.

Insulin Promoting and Counter-Regulatory Hormones

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), from the GI tract, increase prandial insulin release ("incretin" effect).
Amylin inhibits hepatic gluconeogenesis.
Glucagon, catecholamines (e.g., noradrenaline, adrenaline), glucocorticoids (e.g., cortisol) and growth hormone oppose insulin action.

Insulin

Isolated in 1921 by Banting and Best.
Sequenced in 1955 by Sanger.
Gene located on chromosome 11 in humans.
Made from bacteria.
Contains two chains: A chain (21 amino acids) and B chain (30 amino acids).
Only one amino acid differs between pig and human insulin.

Insulin Synthesis

Synthesized in the rough endoplasmic reticulum (RER) of beta islet cells as preproinsulin.
23 amino acids are removed to form proinsulin in the RER.
In the Golgi apparatus, proinsulin is packaged into vesicles.
Cleaved into insulin and C peptide within the vesicles.
Released by exocytosis when blood glucose is high.

Insulin Actions

Hormone of abundance (anabolic hormone).
Actions via insulin receptor include:
- Stimulated glucose uptake in insulin-sensitive tissues (e.g., skeletal muscle and fat; via GLUT4 glucose transporter).
- Stimulated glycogen synthesis.
- Stimulated lipid synthesis.
- Stimulated protein synthesis.
- Stimulated DNA/RNA synthesis.
- Stimulated glycolysis.

Amylin

37 amino acid protein.
Co-released with insulin.
Actions in the central nervous system (CNS).
Inhibits glucagon release.
Slows gastric emptying.
Decreases food intake.
Cleared by kidneys (t½ in circulation about 10 minutes).

Glucagon

Fasting hormone and hormone of energy release (catabolic).
Secreted by alpha islet cells.
29 amino acid linear polypeptide.
Synthesized as preproglucagon.
Degraded by liver and kidneys (t½ in circulation about 6 minutes).
Actions (mainly on liver):
- Increases glycogen breakdown in liver.
- Lipolytic action.
- Increases ketone body formation by liver.
- Increases gluconeogenesis in liver.

Glucose Transporters

Various glucose transporters (GLUTs) are present.
GLUT1-12 are in different tissues and perform different roles in glucose uptake and other processes.

Glucose Transport

Insulin interacts with its receptor, vesicles move to surface and fuse with the plasma membrane.
Increasing the number of glucose transporters in plasma membrane.
When insulin levels drop, glucose transporters are removed from plasma membrane.

Pancreas Summary

The endocrine pancreas mainly produces insulin and glucagon.
Insulin and glucagon control blood glucose.
A lack of insulin leads to diabetes mellitus (can be separated into type 1 and 2).
Diabetes mellitus is treatable with diet, exogenous insulin, and additional hypoglycemic medications (in type 2 diabetes).

Diabetes

Two diseases: diabetes insipidus (posterior pituitary disease) and diabetes mellitus (pancreas disease).
Diabetes mellitus first described by Egyptians in 550 BC.
Diabetes is Greek for siphon (or pass through).
Mellitus was added meaning honey-sweet in 1700s
Two major types of diabetes mellitus: Type 1 and Type 2.

Diabetes Mellitus (Signs & Symptoms)

Polyuria (increased urine volume) & Polydipsia (increased drinking)
Polyphagia (increased appetite)
Hyperglycemia (raised blood sugar)
Glycosuria (glucose in urine)
Ketosis (ketone bodies in blood & urine)*
Acidosis (excess acid in blood)
Rapid weight loss*
Weakness, drowsiness, fatigue.
Skin problems,
Visual problems
Coma.

Criteria for Diagnosing Diabetes

Diabetes symptoms plus:
- A random venous plasma glucose concentration ≥ 11.1 mM or
- A fasting plasma glucose ≥7 mM or
- A 2-hour plasma glucose concentration ≥11.1 mM 2 hours after 75g anhydrous glucose in an oral glucose tolerance test (OGTT).
In certain situations where HbA1c testing is appropriate, HbA1c of 48 mmol/mol (6.5%) is recommended as the cut-off point for diagnosing diabetes.

Causes of Diabetes Mellitus

Autoimmune destruction of beta cells (Type 1 DM).
Excess insulin "antagonists" (e.g., growth hormone)
Insulin receptor problems / insulin resistance (Type 2 DM often).
Defective insulin release (Type 2 DM).
Abnormal insulin produced.
Drug & chemical damage.
Pancreatitis.
Problems with glucose transport.

Types of Diabetes Mellitus

Type 1
- Under 30 years of age.
- Abrupt onset.
- Rare.
- Obesity is uncommon.
- Polyuria is frequent.
- Ketoacidosis may be present.
- Endogenous insulin is negligible.
- ẞ islet cells are few.
- All need insulin therapy.
- Hypoglycemic drugs are not used.
- All need strict diet control.
- 10% of diagnosed cases are type 1.
- Uncommon family history -HLA associated.
- Seasonal trends generally absent.
- Β cell loss is possible due to (viral or chemical).
- Vascular problems include microvascular.
- The ratio of males to females are similar.
Type 2
- Over 40 years of age
- Gradual onset
- Common
- Obesity is common.
- Polyuria is less frequent.
- Ketoacidosis less common.
- Endogenous insulin is present.
- β islet cells are present.
- 20-30% need insulin therapy.
- Hypoglycemic drugs can be used.
- Diet control is important.
- Family history may be a factor.
- Seasonal trends generally not applicable.
- Increased insulin resistance is an associated factor.
- Possible causes are (viral or chemical) and insulin resistance.
- Vascular problems include macrovascular.
- Ratio of males to females tend to be less as compared to males.

Acute Complications of DM

Diabetic ketoacidosis (particularly Type 1 DM)
Hyperglycemia
Hyperosmolar Hyperglycemic State (HHS) (associated with type 2 DM).
Iatrogenic hypoglycemia

Chronic Complications of DM

Retinopathy (eye problems)
Neuropathy (nerve damage)
Nephropathy (kidney problems)
Heart attack & stroke (atherothrombotic problems)
Diabetic foot (circulatory problems)
Gum disease (infection & circulatory problems)
Increased cancer risk (tumorigenesis problems)
Sexual dysfunction (nervous & circulatory problems)

Diabetes Mellitus Therapy

Type 1 DM: exogenous insulin + diet control
Type 2 DM: possible therapies include dietary therapy, drug therapy, and exogenous insulin, or a combination.

Pharmacotherapeutic Management of Diabetes: Classes of Anti-Diabetic Agents

Exogenous insulin preparations (e.g., regular insulin, lispro, glargine).
Inhibitors of glucose absorption (“starch blockers”) (e.g., acarbose).
Enhancers of glucose excretion (e.g., dapagliflozin).
Insulin secretagogues (e.g., sulfonylureas, meglitinides).
Glucagon-like peptide 1 (GLP-1), “incretin”-based therapy (e.g., GLP-1 agonists, DPP-4 inhibitors; incl. sitagliptin, saxagliptin, etc)
Insulin sensitizers (thiazolidinediones, biguanides).

Common Insulin Preparations

Prandial bolus (short/rapid acting) - regular, lispro, aspart, glulisine
Basal (intermediate/long acting)- NPH, glargine, detemir.

Insulin Therapy

Indicated in type 1 and type 2 diabetes insufficiently responsive to diet.
Administered by subcutaneous injection.

Sulphonylureas

Insulin secretagogues.
Examples include tolbutamide, glipizide, and glimepiride.
Bind to SUR1 subunit to block ATP-dependent potassium channels and stimulate glucose-independent insulin release.
Side effects: raised insulin levels, hypoglycemia (particularly in elderly), weight gain, appetite stimulation, GI upset, skin rash, and blood dyscrasias.

Meglitinides (Glinides)

Insulin secretagogues.
Example, repaglinide.
Similar site and mechanism of action as sulphonylureas, but more selective for β cell KATP channels.
Rapid onset and offset.
Less potent than sulphonylureas.
Reduce post-prandial hyperglycemia.
Administered before main meals.
Similar side effect profile to sulphonylureas but a lower risk of hypoglycemia and weight gain.

Biguanides (e.g. Metformin)

Insulin sensitiser.
Inhibitor of hepatic glucose output (predominant action in liver).
Inhibits gluconeogenesis and glycogenolysis.
Inhibitor of glucose absorption from gut
Activates hepatic adenosine 5´-monophosphate (AMP)-activated protein kinase (AMPK)
Increases insulin receptor activity and reduces insulin resistance
Enhances insulin effects in target tissues (e.g. muscle, fat, liver).
Increases insulin dependent glucose uptake (muscle and fat).

Starch Blockers (e.g. Acarbose)

Inhibit α-glucosidase enzymes in gut.
Prevent the breakdown of starch and sucrose into glucose in the gut.
Reduce post-prandial hyperglycemia.
Side effects: GI upset, flatulence, raised triglycerides, aminotransferase elevation.

Thiazolidinediones (TZDs/Glitazones) (e.g. Pioglitazone)

Insulin sensitizers.
Stimulate the nuclear hormone receptor peroxisome proliferator-activated receptor-γ (PPAR-γ).
Predominantly act in muscle.
Reduce peripheral insulin resistance, reduce insulin levels, triglycerides, and free fatty acids.
Potential side effects include weight gain, fluid retention (oedema), anaemia, GI upset, headache, fatigue, potential liver toxicity (needs monitoring).

DPP-4 Inhibitors (Gliptins)

Inhibit dipeptidyl peptidase-4 (DPP-4) enzyme
Incretin enhancers, to elevate GLP-1 level
Enhance glucose-dependent insulin release, reduce glucagon release + hepatic glucose production, and delay gastric emptying.
Lower risk of hypoglycemia (monotherapy).
Main side effects include upper respiratory tract infection, headache, GI upset, nasopharyngitis, raised creatinine levels.

GLP-1 Agonists

Analogues of GLP-1 (DPP-4 resistant)
Mimic actions of GLP-1.
Examples include exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, tirzepatide.
Enhance glucose-dependent insulin release, decrease glucagon release, and delay gastric emptying.
Appetite suppression & weight loss.
Side effects: include GI disturbances, gastroesophageal reflux disease, hypoglycemia, headache, dizziness

Gliflozins

Sodium glucose-linked transporter-2 (SGLT-2) inhibitors.
Prevent proximal tubular reabsorption of filtered glucose from renal filtrate.
Examples include dapagliflozin, canagliflozin, empagliflozin, ertugliflozin.
Low risk of hypoglycemia (monotherapy); weight loss.
Side effects: include polyuria, dehydration, aggravated glycosuria, genital yeast infection, urinary tract infection, skin infection, diabetic ketoacidosis.

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Description

Test your knowledge on diabetes medications including DPP-4 inhibitors and GLP-1 agonists. This quiz covers the mechanisms, effects, and side effects of various classes of diabetes drugs such as sitagliptin, tirzepatide, and sulfonylureas. Challenge yourself to identify different insulin preparations and their classifications.