Podcast
Questions and Answers
What percentage of the pancreatic islets is made up of beta cells?
What percentage of the pancreatic islets is made up of beta cells?
Which hormone is primarily responsible for lowering blood glucose levels?
Which hormone is primarily responsible for lowering blood glucose levels?
In what part of the pancreas do endocrine cells primarily secrete hormones?
In what part of the pancreas do endocrine cells primarily secrete hormones?
What role do glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play in blood glucose regulation?
What role do glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play in blood glucose regulation?
Signup and view all the answers
What is the primary function of the alpha cells in the pancreatic islets?
What is the primary function of the alpha cells in the pancreatic islets?
Signup and view all the answers
Which of the following best describes the lifespan of insulin in circulation?
Which of the following best describes the lifespan of insulin in circulation?
Signup and view all the answers
Which cell type in the pancreatic islets produces somatostatin?
Which cell type in the pancreatic islets produces somatostatin?
Signup and view all the answers
What is the role of ATP-sensitive potassium (KATP) channels in beta cells?
What is the role of ATP-sensitive potassium (KATP) channels in beta cells?
Signup and view all the answers
What is the primary action of metformin?
What is the primary action of metformin?
Signup and view all the answers
What is a common side effect of thiazolidinediones (TZDs) like pioglitazone?
What is a common side effect of thiazolidinediones (TZDs) like pioglitazone?
Signup and view all the answers
Which class of diabetes medications primarily reduces postprandial hyperglycaemia by inhibiting α-glucosidase enzymes?
Which class of diabetes medications primarily reduces postprandial hyperglycaemia by inhibiting α-glucosidase enzymes?
Signup and view all the answers
What is a notable characteristic of repaglinide compared to sulphonylureas?
What is a notable characteristic of repaglinide compared to sulphonylureas?
Signup and view all the answers
Which of the following statements about insulin sensitizers is true?
Which of the following statements about insulin sensitizers is true?
Signup and view all the answers
Which side effect is most commonly associated with metformin?
Which side effect is most commonly associated with metformin?
Signup and view all the answers
What effect do gliptins have on incretin levels?
What effect do gliptins have on incretin levels?
Signup and view all the answers
What does the term 'mellitus' refer to?
What does the term 'mellitus' refer to?
Signup and view all the answers
Which symptom is not commonly associated with diabetes mellitus?
Which symptom is not commonly associated with diabetes mellitus?
Signup and view all the answers
Which type of diabetes mellitus typically has a sudden onset?
Which type of diabetes mellitus typically has a sudden onset?
Signup and view all the answers
What is a common cause of Type 2 diabetes mellitus?
What is a common cause of Type 2 diabetes mellitus?
Signup and view all the answers
What is a significant diagnostic criterion for diabetes?
What is a significant diagnostic criterion for diabetes?
Signup and view all the answers
Which of the following symptoms is especially prevalent in uncontrolled Type 1 diabetes mellitus?
Which of the following symptoms is especially prevalent in uncontrolled Type 1 diabetes mellitus?
Signup and view all the answers
At what age is Type 2 diabetes mellitus most commonly diagnosed?
At what age is Type 2 diabetes mellitus most commonly diagnosed?
Signup and view all the answers
Which of the following can cause insulin resistance in Type 2 diabetes?
Which of the following can cause insulin resistance in Type 2 diabetes?
Signup and view all the answers
What is one of the main distinguishing features of Type 1 diabetes mellitus?
What is one of the main distinguishing features of Type 1 diabetes mellitus?
Signup and view all the answers
Which of the following is not a symptom of diabetes mellitus?
Which of the following is not a symptom of diabetes mellitus?
Signup and view all the answers
What type of hormone is insulin classified as?
What type of hormone is insulin classified as?
Signup and view all the answers
Which of the following statements about glucagon is correct?
Which of the following statements about glucagon is correct?
Signup and view all the answers
What triggers the release of insulin into the bloodstream?
What triggers the release of insulin into the bloodstream?
Signup and view all the answers
What is the role of amylin in the body?
What is the role of amylin in the body?
Signup and view all the answers
Which glucose transporter is primarily influenced by insulin?
Which glucose transporter is primarily influenced by insulin?
Signup and view all the answers
Where is proinsulin converted into insulin?
Where is proinsulin converted into insulin?
Signup and view all the answers
What is one of the main actions of glucagon?
What is one of the main actions of glucagon?
Signup and view all the answers
What happens when blood glucose levels are low?
What happens when blood glucose levels are low?
Signup and view all the answers
Which statement accurately describes the structure of insulin?
Which statement accurately describes the structure of insulin?
Signup and view all the answers
How is diabetes mellitus primarily treated?
How is diabetes mellitus primarily treated?
Signup and view all the answers
Which of the following is a glucagon-like peptide 1 (GLP-1) agonist?
Which of the following is a glucagon-like peptide 1 (GLP-1) agonist?
Signup and view all the answers
What is the primary mechanism of action for sulfonylureas?
What is the primary mechanism of action for sulfonylureas?
Signup and view all the answers
What is the main reason for combining basal and prandial insulin in therapy?
What is the main reason for combining basal and prandial insulin in therapy?
Signup and view all the answers
Which medication is classified as a biguanide?
Which medication is classified as a biguanide?
Signup and view all the answers
What distinguishes thiazolidinediones (TZDs) from other insulin sensitisers?
What distinguishes thiazolidinediones (TZDs) from other insulin sensitisers?
Signup and view all the answers
What is the main side effect associated with sulfonylureas?
What is the main side effect associated with sulfonylureas?
Signup and view all the answers
What type of insulin is considered a prandial bolus preparation?
What type of insulin is considered a prandial bolus preparation?
Signup and view all the answers
Which of the following is NOT a main effect of insulin secretagogues?
Which of the following is NOT a main effect of insulin secretagogues?
Signup and view all the answers
What type of insulin is Neutral Protamine Hagedorn (NPH)?
What type of insulin is Neutral Protamine Hagedorn (NPH)?
Signup and view all the answers
What aspect of insulin therapy must be personalized and adjusted for each patient?
What aspect of insulin therapy must be personalized and adjusted for each patient?
Signup and view all the answers
Study Notes
The Endocrine Pancreas, Diabetes Mellitus & Pharmacotherapeutics
- The pancreas is a flattened organ located posterior and slightly inferior to the stomach
- It is classified as both an endocrine and exocrine gland
- Histologically, it consists of pancreatic islets (or islets of Langerhans) and clusters of cells (acini) which produce digestive enzymes (exocrine cells)
- The pancreas is 5 inches long and consists of head, body, and tail
- 99% of the cells in acini produce digestive enzymes
- Endocrine cells in pancreatic islets produce hormones
Pancreatic Islets (Islets of Langerhans)
- There are 1 to 2 million pancreatic islets per human pancreas (approximately 1-2% of the pancreas' weight)
- Contains 4 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
- Human pancreas contains 8 mg of insulin; secretes 0.5 to 1 mg per day
- Insulin is rapidly destroyed by liver & kidney (half-life in circulation is about 6 minutes)
Regulation of Blood Glucose
- When blood glucose increases, the pancreas secretes insulin to bring glucose levels back to normal
- Glucose enters beta cells via GLUT2 glucose transporter
- ATP synthesis increases
- ATP-sensitive potassium (KATP) channels close
- Insulin is released and reduces blood glucose levels
- When blood glucose is low, the pancreas secretes glucagon to maintain stable levels
- Glucagon increases blood glucose levels
- Insulin and glucagon have opposing actions
Primary Targets for Insulin Action
- Liver
- Skeletal muscle
- Adipose tissue
- Pancreatic alpha cells (to inhibit glucagon release)
- Note: Skeletal muscle and fat depend on insulin for glucose uptake
Insulin Promoting + Counter-Regulatory Hormones
- Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) increase prandial insulin release ("incretin" effect) from the GI tract
- Amylin inhibits hepatic gluconeogenesis
- Glucagon, catecholamines (e.g., noradrenaline, adrenaline), glucocorticoids (e.g., cortisol), and growth hormone oppose insulin action
Regulation of Blood Glucose (Detailed)
- Low blood glucose stimulates alpha cells to release glucagon
- Glucagon acts on hepatocytes to form glucose from glycogen (glycogenolysis) or from lactic acid and amino acids (gluconeogenesis); this raises blood glucose levels to normal
- If blood glucose continues to rise, hyperglycemia inhibits the release of glucagon
- High blood glucose stimulates beta cells to release insulin
- Insulin acts on various body cells to accelerate glucose diffusion, speed glucose conversion to glycogen (glycogenesis), increase amino acid and protein synthesis, and slow glycogenolysis and gluconeogenesis
- If blood glucose continues to fall, hypoglycemia inhibits the release of insulin
Insulin
- Isolated in 1921 by Banting and Best
- Sequenced in 1955 by Sanger
- Gene on chromosome 11 in humans
- Human gene isolated and used to make human insulin from bacteria
- Insulin contains 2 chains (A chain 21 amino acids and B chain 30 amino acids). Only one amino acid differs between pig and human insulin.
Structure of Bovine Insulin
- Detailed structure with amino acid sequences for A and B chains
Synthesis of Insulin
- Insulin is synthesized in the RER of beta islet cells as preproinsulin
- 23 amino acids are removed to form proinsulin in RER
- In Golgi apparatus, proinsulin is packaged into vesicles where it is cleaved into insulin & C peptide
- Released by exocytosis when high blood sugar is present in the blood
Insulin Actions
- Stimulates uptake of glucose in insulin-sensitive tissues, like skeletal muscle and fat (via GLUT4 glucose transporter)
- Stimulates glycogen synthesis
- Stimulates lipid synthesis
- Stimulates protein synthesis
- Stimulates DNA/RNA synthesis
- Stimulates glycolysis
Amylin
- A 37 amino acid protein
- Co-released with insulin
- Actions in the CNS, inhibiting glucagon release; slows gastric emptying; decreases food intake
- Cleared by kidneys (half-life of approximately 10 minutes)
Glucagon
- Fasting hormone & hormone of energy release (catabolic)
- Secreted by alpha islet cells
- A 29 amino acid linear polypeptide synthesized as preproglucagon and degraded by the liver and kidneys (half-life approximately 6 minutes)
- Primarily acts on the liver to increase glycogen breakdown, lipolysis, ketone body formation, and gluconeogenesis
Insulin Actions (Synthesis/Breakdown Summary Table)
- Table summarizing the effects of insulin on synthesis and breakdown of protein, lipids, glycogen, DNA/RNA, glucose (gluconeogenesis) and glycolysis, and on the liver.
Glucose Transporters
- Table listing glucose transporter types, their tissue expression, and their role.
Glucose Transport Mechanism
- Detailed explanation of glucose transport, including the roles of vesicles and insulin receptors, with diagrams.
Pancreas Summary
- The endocrine pancreas mainly produces insulin and glucagon
- Insulin and glucagon control blood glucose levels
- Lack of insulin results in diabetes mellitus
- Diabetes mellitus can be divided into Type 1 and Type 2
- Diabetes mellitus can be treated with diet, exogenous insulin, and various hypoglycemic drugs in Type 2 DM.
Diabetes: Two Diseases
- Diabetes insipidus (posterior pituitary disease)
- Diabetes mellitus (pancreas disease)
- Diabetes mellitus was first described by the Egyptians in 550 BC
- "Diabetes" means "pass through" in Greek, referring to the excessive urination
- "Mellitus" meaning "honey sweet" was added to the name in 1700s
Two Major Types of Diabetes Mellitus
- Type 1
- Type 2
Diabetes Mellitus Signs and Symptoms
- Main signs and symptoms of diabetes, including:
- Polyuria
- Polydipsia
- Polyphagia
- Hyperglycemia
- Glycosuria
- Ketosis
- Acidosis
- Rapid weight loss
- Weakness, drowsiness, and fatigue
- Skin problems
- Visual problems
- Coma
Criteria for Diagnosing Diabetes
- Diabetes symptoms plus a random venous glucose concentration ≥ 11.1 mM or a fasting plasma glucose ≥ 7mM or a 2-hour plasma glucose concentration ≥11.1 mM 2 hours after a 75g glucose tolerance test (OGTT).
- An HbA1c of 48mmol/mol (6.5%) may be used for diagnosis.
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)
- Defective insulin release (Type 2 DM)
- Abnormal insulin produced
- Drug or chemical damage
- Pancreatitis
- Problems with glucose transport.
Types of Diabetes Mellitus (Detailed Comparison)
- Table comparing Type 1 and Type 2 diabetes based on onset, type of onset, obesity, symptoms, ketosis, endogenous insulin, islet cells, insulin therapy, hypoglycemic drugs, diet, family history, HLA-associated, seasonal trends, possible causes, vascular problems, sex ratio.
Diabetes Mellitus: Acute Complications
- Diabetic ketoacidosis (particularly uncontrolled Type 1 DM)
- Hyperglycemia
- Hyperosmolar Hyperglycemic State (HHS) (associated with Type 2 DM)
- Iatrogenic hypoglycemia
Diabetes Mellitus: Chronic Complications
- 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:
- Dietary therapy (especially if overweight)
- Drug therapy + diet control
- Exogenous insulin + diet control
Pharmacotherapeutics of Anti-Diabetic Agents
- Exogenous insulin preparations (e.g., regular insulin, insulin lispro, insulin glargine)
- Inhibitors of glucose absorption ("starch blockers") (e.g., acarbose)
- Enhancers of glucose excretion (e.g., dapagliflozin)
- Insulin secretagogues (e.g., tolbutamide, glipizide, repaglinide)
- Glucagon-like peptide-1 (GLP-1), "incretin"-based therapy (e.g., exenatide, liraglutide)
- Insulin sensitizers (e.g., pioglitazone, metformin)
- Starch blockers (e.g., acarbose)
Common Insulin Preparations
- Prandial bolus (short/rapid acting): regular, lispro, aspart, glulisine
- Basal (intermediate/long acting): neutral protamine hagedorn (NPH), glargine, detemir
Insulin Therapy
- Indicated in Type 1 DM + Type 2 DM insufficiently responsive to diet and oral hypoglycaemic agents
- Administered by subcutaneous injection
- Typically, basal preparation (constant low-level background insulin) + prandial bolus preparations (before meals)
- Personalised regimen (e.g., preparation, dosage, frequency) , adjusted to patient's activity, meals, and blood glucose
Sulphonylureas
- Insulin secretagogues; stimulate islet B cells to release insulin (in a glucose independent manner) e.g., tolbutamide, glipizide, glimepiride
- Bind to SUR1 subunit on ATP-dependent potassium (KATP) channel leading to channel blockade, depolarization then insulin release
- Side effects include hypoglycaemia, weight gain, and digestive problems
Meglitinides (Glinides)
- Insulin secretagogues e.g., repaglinide
- Similar action site & mechanism to sulphonylureas but more selective for beta-cell KATP channels
- Rapid onset & offset; short-duration action
- Less potent than sulphonylureas; reduce postprandial hyperglycaemia; typically administered before meals
- Side effects similar to sulphonylureas but lower risk of hypoglycaemia and weight gain
Biguanides
- Insulin sensitiser (e.g., Metformin)
- Inhibits hepatic glucose output (predominantly in liver); inhibits glucose absorption from gut
- Activates hepatic adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)
- Increases insulin receptor activity; reduces insulin resistance
- Enhances insulin effects in target tissues; increases insulin-dependent glucose uptake by muscle and fat
- Low risk of hypoglycaemia (as monotherapy), no weight gain (some weight loss possible)
- Side effects include gastrointestinal upset, altered taste, decreased appetite, vitamin B12 deficiency, and lactic acidosis
Starch Blockers
- Inhibit a-glucosidase enzymes in the gut; block starch and sucrose breakdown; reduce/delay glucose absorption from the gut e.g., acarbose
- Few side effects; no weight gain
- Low/no risk of hypoglycaemia (as monotherapy)
- Reduces postprandial hyperglycaemia
- Common side effects: GI upset, flatulence, aminotransferase elevation, raised triglycerides
Thiazolidinediones (TZDs)/Glitazones
- Insulin sensitiser (e.g., Pioglitazone)
- Stimulates nuclear hormone receptor PPAR-γ; predominant action in muscle
- Reduces peripheral insulin resistance; reduces insulin levels, triglycerides, and free fatty acids
- Side effects: weight gain, fluid retention, oedema, anaemia, gastrointestinal upset, headache, fatigue, potential liver toxicity (monitor), and possible increased LDL cholesterol
GLP-1 agonists
- Analogues of GLP-1 (DPP-4 resistant)
- Mimic actions of GLP-1 e.g., exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, tirzepatide
- Enhances glucose-dependent insulin release; decrease glucagon release; increase hepatic glucose production and delay gastric emptying
- Appetite suppression; weight loss
- Side effects: gastrointestinal disturbances, gastroesophageal reflux disease, hypoglycemia, headache, and dizziness
Glinides
- Sodium glucose-linked transporter-2 (SGLT-2) inhibitors; e.g., dapagliflozin, canagliflozin, empagliflozin, ertugliflozin
- Prevent proximal tubular reabsorption of filtered glucose from the renal filtrate
- Low risk of hypoglycemia; weight loss
- Side effects include polyuria, dehydration, aggravated glycosuria, genital and urinary tract infections, skin infections, increased risk of diabetic ketoacidosis
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on the endocrine functions of the pancreas and the roles of various cell types in blood glucose regulation. This quiz covers key concepts such as insulin secretion, the function of beta and alpha cells, and the action of diabetes medications. Perfect for students studying endocrinology and diabetes management.
