Glucose Homeostasis Flashcards
What is glucose particularly important for?
Glucose is an important energy substrate. This is particularly true for the central nervous system: If the blood glucose concentration falls much below normal levels of 4-5 mmol/L (hypoglycaemia), then cerebral function is increasingly impaired. If blood glucose concentration <2 mmol/L, unconsciousness, coma and ultimately death can result.
What regulates glucose levels?
Multiple hormones: Insulin responsible for reducing blood glucose while glucagon, cortisol, GH and catecholamines are responsible for increasing it. Persistent hyperglycaemia results in diabetes mellitus.
What are the different diabetes mellitus phenotypes and their prevalence?
Maturity onset diabetes of the young (MODY), Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM). T2 most common.
What are the pancreatic islets of Langerhans?
The pancreas is a retroperitoneal structure. Most of pancreas generates exocrine secretions via duct to small intestine while small clumps of cells within pancreatic tissue called Islets of Langerhans produce the hormones involved in blood glucose control.
What are the key structural components of the islets of Langerhans?
Three main cell types present: alpha cells producing glucagon, beta cells producing insulin and delta cells producing somatostatin. Gap junctions are the gaps along edges of cells that allow small molecules to pass directly between cells. Tight junctions occur at the very corner between two cells that create small intercellular spaces. This allows paracrine communication between cells and to communicate hormone levels with one another so each can produce an appropriate amount of hormone.
What is the action of the pancreatic hormones?
Insulin reduces blood glucose levels while glucagon increases it. Somatostatin inhibits the functioning of both insulin and glucagon. Insulin is also responsible for growth and development especially in the foetal stage.
How is insulin secretion triggered?
Some amino acids, GI hormones and presence of glucagon as well as sympathetic nervous system activity via beta cell route and parasympathetic nervous system activity can lead to increased insulin secretion, However, somatostatin activity and sympathetic innervaton via alpha route can inhibit it.
What does insulin cause?
Build up of glycogen stores, breakdown of glucose and increased uptake of glucose via GLUT4. Additional actions include increase of protein synthesis and reduction in breakdown of fat.
What is the response to a reduction in blood glucose?
A reduction in blood glucose, some amino acids, some GI hormones, SNS activity via the alpha route and PNS activity can all trigger glucagon secretion. Somatostatin and insulin inhibit it.
How does glucagon act to increase blood glucose?
It increases amino acid transport to the liver as well as lipolysis, providing substrate for gluconeogenesis. This coupled with hepatic glycogenolysis increases blood glucose levels.
How does the beta cell in the islets sense glucose level?
GLUT 2 transporter on islet membrane has a high affinity for glucose but is not insulin sensitive - hence it allows all the glucose in, thus intracellular glucose levels mimic the external environment. Here, hexokinase IV (glucokinase) acts on the glucose converting it to glucose-6-phosphate. This is the main glucose sensor as it is the rate-limiting step and not subject to negative feedback.
How does beta cell release insulin?
Glucose-6-phosphate is respired to produce ATP which inhibits efflux of potassium causing membrane depolarisation. This stimulates an influx of calcium which causes the stored vesicles of insulin to be exocytosed.
What do C-peptide levels tell us about insulin?
Pro-insulin is cleaved to form insulin and C-peptide hence, provides a good estimate regarding insulin levels in bloodstream.
