L4 - Glucose and Diabetes Flashcards
What are the acinar cells in the pancreas?
Acinar cells are found in the exocrine portion of the pancreas.
They secrete digestive enzymes (e.g., amylase, lipase, trypsinogen) into the pancreatic duct, which leads to the small intestine for digestion of carbohydrates, fats, and proteins.
What are the Islets of Langerhans?
The Islets of Langerhans are clusters of endocrine cells located in the pancreas.
They are responsible for producing hormones that regulate glucose metabolism, including:
Alpha cells: Secrete glucagon, which increases blood glucose levels.
Beta cells: Secrete insulin, which decreases blood glucose levels.
Delta cells: Secrete somatostatin, which inhibits insulin and glucagon release.
PP cells: Secrete pancreatic polypeptide, which regulates pancreatic secretion and appetite.
What are the functions of the cells in the Islets of Langerhans?
A:
β cells: Secrete insulin, which lowers blood glucose by promoting glucose uptake in cells.
α cells: Secrete glucagon, which raises blood glucose by stimulating the liver to release glucose.
δ cells: Secrete somatostatin, which inhibits insulin and glucagon release and regulates the digestive process.
PP cells: Secrete pancreatic polypeptide, which increases gastric enzyme secretion and decreases gastric motility
What is the role of acinar cells in the pancreas?
Acinar cells are part of the exocrine pancreas.
They produce digestive enzymes (e.g., amylase, lipase, trypsinogen) that are secreted into the pancreatic duct, which carries them to the small intestine for digestion of nutrients.
How are the Islets of Langerhans and acinar cells functionally different in the pancreas?
Islets of Langerhans are part of the endocrine pancreas and secrete hormones like insulin, glucagon, and somatostatin into the bloodstream for glucose regulation.
Acinar cells are part of the exocrine pancreas and secrete digestive enzymes into ducts leading to the small intestine for nutrient digestion.
What is the role of insulin in glucose homeostasis?
Insulin lowers blood glucose levels by promoting:
Fat synthesis (lipogenesis)
Protein synthesis
Glycogen synthesis (glycogenesis)
Glucose uptake into cells, especially in muscle and adipose tissue.
What is the role of glucagon in glucose homeostasis?
Glucagon raises blood glucose levels by stimulating:
Gluconeogenesis (glucose production from non-carbohydrate sources) in the liver
Glycogen breakdown (glycogenolysis) to release glucose
Fatty acid catabolism (lipolysis) for energy production.
How do insulin and glucagon work together in maintaining glucose homeostasis?
Insulin and glucagon act in opposition to maintain blood glucose levels:
Insulin promotes the storage of glucose (as glycogen), fat, and protein when glucose levels are high.
Glucagon promotes the release of glucose by stimulating gluconeogenesis, glycogen breakdown, and fat catabolism when glucose levels are low.
What are the blood glucose levels for hypoglycaemia, normoglycaemia, and hyperglycaemia?
Hypoglycaemia: < 3.5 mmol/L
Normoglycaemia: 3.5 - 7.5 mmol/L
Hyperglycaemia: > 7.5 mmol/L
How does the body respond to hypoglycaemia?
Hypoglycaemia (< 3.5 mmol/L) triggers:
Increased glucagon release from α cells
Increased glycogenolysis (glycogen breakdown)
Increased gluconeogenesis (glucose production from non-carbohydrate sources)
Increased proteolysis (protein breakdown for glucose synthesis)
Decreased glucose uptake into cells.
How does the body respond to hyperglycaemia (post-prandial)?
Hyperglycaemia (> 7.5 mmol/L) triggers:
Increased insulin release from β cells
Increased glycolysis (glucose breakdown for energy)
Increased glycogenesis (glycogen formation)
Increased glucose uptake into cells for energy storage.
How does the body respond to starvation in terms of glucose homeostasis?
During starvation:
Increased glucagon release from α cells
Increased glycogenolysis and gluconeogenesis to maintain blood glucose levels
Decreased glucose uptake into cells
Increased proteolysis to generate amino acids for gluconeogenesis.
What are the key steps in glucagon release from pancreatic α cells?
ATP levels increase (due to low glucose levels)
This causes K+ channels (KATP) to close, leading to membrane depolarisation
Depolarisation activates voltage-gated Ca2+ channels, allowing Ca2+ to enter the cell
The increase in Ca2+ triggers the release of glucagon from α cells.
What is the role of GLUT-1 in glucagon release?
GLUT-1 facilitates glucose uptake into pancreatic cells.
Low glucose levels lead to reduced GLUT-1 activity, triggering the signalling cascade for glucagon release.
How does membrane depolarisation lead to glucagon release?
Depolarisation occurs when KATP channels close due to low ATP levels, resulting in reduced K+ efflux.
This depolarisation opens voltage-gated Ca2+ channels, allowing Ca2+ influx, which initiates the release of glucagon from α cells.
What are the key steps in glucagon signalling in hepatocytes, adipocytes, and skeletal muscle?
Glucagon binds to the glucagon receptor on the target cell.
This activates Gs (G-protein), which stimulates adenylyl cyclase (AC).
AC increases cAMP levels, which activates protein kinase A (PKA).
In hepatocytes, this leads to increased gluconeogenesis and glycogenolysis, and decreased glycogenesis.
In adipocytes, glucagon stimulates lipolysis, increasing fatty acid release.
In skeletal muscle, glucagon has minimal direct effects but can influence metabolism via systemic effects.
What is the role of cAMP and PKA in glucagon signalling?
cAMP is produced in response to glucagon receptor activation.
cAMP activates PKA (protein kinase A), which then phosphorylates various enzymes involved in glycogen breakdown (glycogenolysis), glucose production (gluconeogenesis), and inhibition of glycogen synthesis (glycogenesis).
How does glucagon affect glycogen metabolism?
A:
Glucagon activates glycogenolysis (breakdown of glycogen to glucose) by increasing cAMP and PKA activity.
Glycogen synthesis (glycogenesis) is inhibited by glucagon.
Gluconeogenesis is stimulated to produce more glucose from non-carbohydrate sources.
What are the clinical uses of glucagon?
Glucagon is used for emergency treatment of hypoglycaemia (low blood sugar) with reduced consciousness.
It can be administered via subcutaneous, intramuscular injection, or intravenous infusion.
What are the adverse effects of glucagon?
The common adverse effects include nausea and vomiting.
What is the mechanism of insulin release from pancreatic β cells?
A:
Glucose enters β cells through GLUT-2 transporters.
ATP production from glucose metabolism causes the K+ATP channels to close.
This leads to membrane depolarisation, which opens voltage-gated Ca2+ channels.
The influx of Ca2+ triggers the release of insulin.
How do sulfonylurea drugs affect insulin release?
A:
Sulfonylurea drugs bind to the sulfonylurea receptor on K+ATP channels, causing them to close.
This induces membrane depolarisation, leading to Ca2+ influx and subsequent insulin release.
What are the actions of insulin on glucose metabolism?
Increase in glycogenesis (glycogen synthesis).
Increase in glycolysis (glucose breakdown for energy).
Decrease in gluconeogenesis (glucose production from non-carbohydrate sources).
Increase in glucose uptake by cells.
How does insulin affect lipid metabolism?
Increase in lipogenesis (fatty acid and triglyceride synthesis).
Decrease in lipolysis (fat breakdown).
How does insulin influence protein metabolism?
Increase in protein synthesis (building proteins from amino acids).
What is the role of insulin in skeletal muscle and adipose tissue glucose homeostasis?
Insulin binds to the insulin receptor, triggering a cascade that activates IRS (Insulin Receptor Substrate) and PI3K (Phosphoinositide 3-Kinase).
This activation leads to the phosphorylation of Akt, which facilitates the translocation of GLUT-4 (glucose transporter) vesicles to the cell surface, increasing glucose uptake.
What is the function of GLUT-4 in skeletal muscle and adipose tissue?
GLUT-4 transports glucose into skeletal muscle and adipose tissue cells in response to insulin stimulation.
What signalling pathway is involved in insulin-mediated glucose uptake in muscle and adipose tissue?
Insulin binds to the insulin receptor, activating the IRS/PI3K/Akt signalling pathway, leading to GLUT-4 translocation and increased glucose uptake.
How does insulin regulate glucose homeostasis in the liver?
Insulin binds to its receptor on hepatocytes, activating the IRS/PI3K/Akt pathway.
This pathway reduces glycogenolysis (breakdown of glycogen) and gluconeogenesis (glucose production), promoting glucose uptake via GLUT-2 and conversion to glucose-6-phosphate by glucokinase.
What is the role of GLUT-2 in hepatocytes during insulin-mediated glucose uptake?
GLUT-2 facilitates the uptake of glucose into hepatocytes in response to insulin, enabling the conversion of glucose to glucose-6-phosphate.
How does insulin affect glycogenolysis and gluconeogenesis in the liver?
Insulin inhibits glycogenolysis (breakdown of glycogen) and gluconeogenesis (production of glucose) in the liver, promoting glucose storage and decreased glucose output.
What is the role of glucokinase in glucose metabolism in the liver?
Glucokinase in hepatocytes phosphorylates glucose to form glucose-6-phosphate, which can be used in glycogen synthesis or other metabolic pathways.
What are the main types of diabetes?
Type 1: Autoimmune disease, insulin deficient, often young onset, insulin dependent.
Type 2: Metabolic disorder, insulin resistance with some insulin deficiency, typically older onset, not enough insulin production.
Gestational diabetes: Occurs in the 2nd/3rd trimester, risk to both parent and child.
What is the main cause of Type 1 diabetes?
Type 1 diabetes is an autoimmune disorder that leads to the destruction of insulin-producing beta cells in the pancreas, causing insulin deficiency.
How does Type 2 diabetes differ from Type 1 diabetes in terms of insulin production?
In Type 1 diabetes, there is an insulin deficiency due to beta-cell destruction.
In Type 2 diabetes, there is insulin resistance and some insulin deficiency, but the pancreas may still produce insulin.
What are the risks associated with gestational diabetes?
Gestational diabetes poses risks to both the parent and the child, including potential complications during pregnancy and delivery.
What is Type 2 Diabetes Mellitus (T2DM)?
T2DM is a metabolic disorder characterised by insulin resistance and, eventually, insulin deficiency. It usually occurs in older adults but can affect younger individuals, particularly with obesity or sedentary lifestyle.
What is the main pathophysiology behind Type 2 Diabetes?
In T2DM, there is insulin resistance, where the body’s cells (particularly muscle and adipose tissue) do not respond effectively to insulin. Over time, this leads to increased blood glucose levels and eventual insulin secretion deficiency.
What are the risk factors for developing Type 2 Diabetes?
Obesity, particularly abdominal fat.
Physical inactivity.
Family history of diabetes.
Age (greater risk in individuals over 45).
Poor diet, especially diets high in sugars and fats.
Hypertension and dyslipidaemia.
What are the main clinical manifestations of Type 2 Diabetes?
Increased thirst (polydipsia).
Increased urination (polyuria).
Fatigue.
Blurred vision.
Slow healing wounds.
Frequent infections.
How is Type 2 Diabetes diagnosed?
A:
Through blood tests showing:
Fasting plasma glucose (FPG) ≥ 7.0 mmol/L.
Oral glucose tolerance test (OGTT): 2-hour plasma glucose ≥ 11.1 mmol/L.
HbA1c ≥ 6.5% (48 mmol/mol).
What is the role of insulin resistance in the development of Type 2 Diabetes?
Insulin resistance reduces the effectiveness of insulin in muscle, adipose tissue, and liver, leading to impaired glucose uptake, increased glucose production by the liver, and ultimately hyperglycaemia.
What are the treatment options for Type 2 Diabetes?
Lifestyle modifications: Weight loss, improved diet, and increased physical activity.
Medications:
Metformin (first-line treatment).
Sulfonylureas, DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors.
Insulin therapy may be required in advanced stages.
What are the main metabolic defects in Type 2 Diabetes Mellitus (T2DM)?
A:
Obesity: Excess fat leads to increased free fatty acids (FFAs) and adipokines, which contribute to insulin resistance and inflammation.
Insulin resistance: Cells in muscle, adipose tissue, and the liver do not respond properly to insulin, impairing glucose uptake and causing elevated blood glucose levels.
Increased FFAs: Elevated free fatty acids lead to lipid accumulation in non-adipose tissues, further worsening insulin resistance.
Adipokines and inflammation: Imbalance in adipokines (hormones secreted by fat cells) promotes inflammatory pathways and insulin resistance.
How does obesity contribute to insulin resistance in Type 2 Diabetes?
Obesity, particularly visceral fat, increases the release of free fatty acids (FFAs) and adipokines. These molecules promote inflammation and disrupt the insulin signalling pathway, leading to decreased insulin sensitivity and increased blood glucose levels.
What role do free fatty acids (FFAs) play in insulin resistance in Type 2 Diabetes?
FFAs can accumulate in muscle and liver cells, leading to lipotoxicity. This inhibits insulin signalling pathways, contributing to insulin resistance and reduced glucose uptake by cells, which increases blood glucose levels.
How do adipokines contribute to insulin resistance and inflammation in Type 2 Diabetes?
Adipokines are hormones secreted by adipose tissue. In obesity, an imbalance of these hormones (e.g., increased resistin and decreased adiponectin) promotes low-grade inflammation and disrupts insulin signalling, further exacerbating insulin resistance and contributing to the development of T2DM.
What is the role of inflammation in the pathophysiology of Type 2 Diabetes?
Chronic low-grade inflammation in adipose tissue, driven by increased FFAs and altered adipokine secretion, activates inflammatory pathways that interfere with insulin signalling and increase insulin resistance, contributing to the progression of Type 2 Diabetes.
