Glucose, Glucagon and Insulin & Diabetes Pathogenesis

A collection of vocabulary flashcards based on key concepts from a lecture on glucose metabolism, insulin, glucagon, and diabetes.

Glucose Homeostasis

The mechanisms that regulate blood glucose levels to maintain balance in the body.

Insulin

A polypeptide hormone produced by β cells of the pancreas; promotes glucose uptake and storage as glycogen.

Glucagon

A hormone secreted by α cells of the pancreas that promotes the release of glucose from glycogen stores.

Type 1 Diabetes

An autoimmune condition characterized by the destruction of pancreatic β cells leading to insulin deficiency.

Type 2 Diabetes

A metabolic disorder resulting from insulin resistance in tissues and usually associated with obesity.

Islets of Langerhans

Clusters of endocrine cells in the pancreas; contains α, β, and δ cells that secrete glucagon, insulin, and somatostatin respectively.

Glycogenolysis

The process of converting glycogen into glucose, primarily stimulated by glucagon.

Gluconeogenesis

The synthesis of glucose from non-carbohydrate precursors, important during fasting.

GLUT4

A glucose transporter that facilitates glucose uptake into cells, particularly muscle and fat cells, in response to insulin.

Diabetes Mellitus

A chronic condition characterized by high blood glucose levels due to insufficient insulin secretion or resistance.

What is glucose homeostasis?

Glucose homeostasis is the physiological regulation of blood glucose levels to maintain a constant energy supply; particularly for the brain.

Where is dietary glucose absorbed?

Dietary glucose is absorbed from the small intestine into the bloodstream.

What are the two functional components of the pancreas?

The pancreas has an exocrine component for digestion and an endocrine component containing the islets of Langerhans.

What is the function of the endocrine pancreas?

The endocrine pancreas secretes hormones directly into the bloodstream to regulate metabolism.

Which pancreatic cells secrete insulin?

Beta cells of the pancreatic islets secrete insulin.

Which pancreatic cells secrete glucagon?

Alpha cells of the pancreatic islets secrete glucagon.

Which pancreatic cells secrete somatostatin?

Delta (δ) cells of the pancreatic islets secrete somatostatin.

What is the role of somatostatin in glucose regulation?

Somatostatin inhibits the secretion of both insulin and glucagon to fine-tune glucose balance.

Where does pancreatic blood drain first?

Pancreatic hormones enter the hepatic portal vein and reach the liver before systemic circulation.

Why is the liver central to glucose regulation?

The liver is the first organ exposed to portal glucose and insulin and regulates storage and release.

Where is glucose stored in the body?

Glucose is stored as glycogen in the liver and skeletal muscle.

Why must blood glucose be maintained between meals?

The brain depends continuously on circulating glucose for energy.

Which hormone predominates in the fed state?

Insulin predominates in the fed state.

Which hormone predominates during fasting?

Glucagon predominates during fasting.

How is insulin synthesised in beta cells?

Insulin is synthesised as proinsulin and then processed to active insulin.

How is proinsulin converted to active insulin?

Prohormone convertases remove the C-peptide to form active insulin.

What is the structure of active insulin?

Active insulin consists of two polypeptide chains linked by disulfide bonds.

Where is insulin stored before secretion?

Insulin is stored in secretory granules within beta cells.

What triggers insulin secretion?

An increase in blood glucose concentration triggers insulin secretion.

What are the two phases of insulin secretion?

Insulin secretion has a rapid first phase from stored granules followed by a slower second phase of newly synthesised insulin.

Why is the first phase of insulin secretion important?

The first phase rapidly limits the post-meal rise in blood glucose.

Which transporter allows glucose entry into beta cells?

GLUT2 transports glucose into beta cells.

Is GLUT2 insulin-dependent?

GLUT2 is not insulin-dependent and responds to glucose concentration.

What intracellular change links glucose to insulin release?

Increased intracellular ATP links glucose metabolism to insulin release.

What happens to ATP-sensitive potassium channels when ATP rises?

They close; causing membrane depolarisation.

What occurs after membrane depolarisation in beta cells?

Voltage-gated calcium channels open.

What directly triggers insulin exocytosis?

Calcium influx triggers insulin granule exocytosis.

What enzyme degrades circulating insulin?

Insulinase degrades circulating insulin.

Why does insulin have a short duration of action?

Insulin is rapidly broken down in the liver; muscle and kidney.

What type of receptor does insulin bind to?

Insulin binds to a receptor tyrosine kinase.

What happens after insulin binds its receptor?

The receptor undergoes autophosphorylation and activates intracellular signalling pathways.

Which intracellular pathway mediates insulin’s metabolic effects?

The PI3K–Akt signalling pathway mediates most metabolic effects.

Which tissues respond strongly to insulin?

Liver; skeletal muscle and adipose tissue respond strongly to insulin.

How does insulin increase glucose uptake in muscle?

Insulin stimulates translocation of GLUT4 transporters to the cell membrane.

Where is GLUT4 located without insulin?

GLUT4 remains in intracellular vesicles when insulin is absent.

How does insulin promote glycogen synthesis?

Insulin activates glycogen synthase by inhibiting glycogen synthase kinase.

How does insulin influence fat metabolism?

Insulin promotes lipogenesis and inhibits lipolysis.

How does insulin influence protein metabolism?

Insulin stimulates protein synthesis through activation of mTOR pathways.

Why can the brain take up glucose without insulin?

Brain cells use insulin-independent glucose transporters.

What type of receptor does glucagon bind?

Glucagon binds to a Gs protein-coupled receptor.

Which pathway does glucagon activate?

Glucagon activates the cAMP–protein kinase A pathway.

What is the primary effect of glucagon in the liver?

Glucagon stimulates glycogen breakdown and glucose release.

What is gluconeogenesis?

Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources such as amino acids.

When is gluconeogenesis important?

It is important during prolonged fasting when glycogen stores are depleted.

How does glucagon affect adipose tissue?

Glucagon promotes fat breakdown and fatty acid release.

How does exercise influence glucose regulation?

Exercise promotes GLUT4 translocation independently of insulin and increases glucagon secretion.

How does adrenaline raise blood glucose?

Adrenaline activates beta-adrenergic receptors; increasing cAMP and glycogen breakdown.

What is diabetes mellitus?

Diabetes mellitus is a disorder characterised by chronic dysregulation of blood glucose.

Why does glucose appear in urine in diabetes?

Glucose appears in urine when renal transporters become saturated.

Why does diabetes cause dehydration?

High tubular glucose increases osmolarity, reducing water reabsorption

What causes type 1 diabetes?

Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells.

What is the fundamental defect in type 1 diabetes?

Type 1 diabetes results in absolute insulin deficiency.

Why does type 1 diabetes cause ketoacidosis?

Low insulin and high glucagon increase fatty acid oxidation and ketone production.

What is the goal of insulin therapy in type 1 diabetes?

To replace missing insulin and mimic physiological secretion.

Why must insulin injection sites be rotated?

Rotation prevents lipohypertrophy and ensures consistent absorption.

What is lipohypertrophy?

Lipohypertrophy is localised fat accumulation at repeated injection sites.

What does glycosylated haemoglobin indicate?

Glycosylated haemoglobin reflects long-term blood glucose exposure.

What is the primary defect in type 2 diabetes?

Type 2 diabetes is primarily caused by insulin resistance.

How do beta cells initially compensate in type 2 diabetes?

Beta cells increase insulin secretion to overcome resistance.

What leads to progression in type 2 diabetes?

Progression occurs when beta cells fail to maintain compensatory insulin secretion.

How do fatty acids impair insulin signalling?

Fatty acid metabolites interfere with insulin receptor signalling pathways.

What is adiponectin?

Adiponectin is an adipose-derived hormone that improves insulin sensitivity.

How does obesity affect adiponectin?

Obesity reduces adiponectin levels.

How do thiazolidinediones improve insulin sensitivity?

They activate PPARγ to enhance insulin responsiveness in adipose tissue.

How does metformin reduce blood glucose?

Metformin activates AMPK and reduces hepatic glucose production.

How do sulfonylureas stimulate insulin release?

Sulfonylureas close ATP-sensitive potassium channels in beta cells.

How do SGLT2 inhibitors lower blood glucose?

They block renal glucose reabsorption in the proximal tubule.

What enzyme converts glucose to glucose-6-phosphate in the liver?

Glucokinase converts glucose to glucose-6-phosphate.

Why is glucose-6-phosphate important?

It is a precursor for glycogen synthesis and glycolysis.

How does chronic hyperglycaemia damage blood vessels?

Chronic hyperglycaemia increases oxidative stress and protein glycation.

What are advanced glycation end products (AGEs)?

AGEs are proteins modified by glucose that contribute to vascular damage.

How do AGEs affect blood vessels?

AGEs crosslink collagen; thicken basement membranes and promote inflammation.

What complications can result from chronic hyperglycaemia?

Chronic hyperglycaemia can lead to microvascular and macrovascular damage.

What is the normal blood glucose concentration and why is it maintained?

Approximately 5 mmol/L and it is tightly regulated primarily to ensure a constant supply of glucose to the brain which relies almost exclusively on glucose for energy

What are the main sources of blood glucose?

Dietary carbohydrate absorption glycogenolysis from liver and muscle and gluconeogenesis from amino acids and fatty acids during fasting

What happens to glucose after ingestion of a carbohydrate-rich meal?

Glucose is absorbed from the GI tract enters circulation increases blood glucose stimulates insulin release then is taken up by tissues used for ATP production stored as glycogen in liver and muscle or converted to fatty acids if in excess

What is the role of the liver in glucose homeostasis?

The liver is the first organ exposed to glucose and insulin via the hepatic portal vein and acts as the main regulator by storing glucose as glycogen and releasing it during fasting

Describe what happens to blood glucose between meals.

Blood glucose would fall due to lack of absorption but is maintained at ~5 mmol/L by glycogenolysis in the liver and later gluconeogenesis

Why can most tissues survive without glucose but the brain cannot?

Most tissues can switch to fatty acid metabolism but the brain cannot utilise fatty acids and depends on glucose

Describe the full mechanism of glucose-stimulated insulin secretion.

Glucose enters beta cells via GLUT2 transporter which is insulin-independent glucose is metabolised to produce ATP increased ATP closes ATP-sensitive potassium channels causing membrane depolarisation depolarisation opens voltage-gated calcium channels calcium enters the cell increased intracellular calcium triggers exocytosis of insulin-containing vesicles

Why is GLUT2 important in beta cells?

GLUT2 is insulin-independent and always active allowing beta cells to sense blood glucose levels directly

What are ATP-sensitive potassium channels and their role?

They are channels that are open at low ATP levels and close when ATP rises leading to depolarisation which is essential for insulin secretion

What triggers opening of calcium channels in beta cells?

Membrane depolarisation caused by closure of ATP-sensitive potassium channels

What are the two phases of insulin secretion?

First phase is rapid release of pre-stored insulin from secretory granules second phase is slower sustained secretion due to new insulin synthesis

Why is insulin difficult to measure directly in blood?

It has a very short half-life of around 6 minutes and is rapidly degraded by insulinase

Why is C-peptide used clinically?

C-peptide is released in equal amounts to insulin but is more stable in circulation so it reflects endogenous insulin production

Describe insulin synthesis in beta cells.

Insulin is synthesised as preproinsulin then processed in the Golgi apparatus into proinsulin prohormone convertases remove the C-peptide producing active insulin composed of A and B chains linked by disulfide bonds

What is the structure of insulin?

It consists of two polypeptide chains A chain of 30 amino acids and B chain of 21 amino acids connected by disulfide bonds

Where is insulin stored before secretion?

In secretory granules within beta cells along with proinsulin and C-peptide

Describe the insulin receptor structure and activation.

It is a dimeric tyrosine kinase receptor composed of alpha and beta subunits insulin binding causes dimerisation and autophosphorylation of tyrosine residues activating intracellular signalling