Diabetes And Insulin Flashcards
Describe why blood glucose is regulated and which hormones are the main effectors
Glucose is the only fuel for the brain and therefore very important. The body mostly cares about maintaining it above a threshold than lowering it. Under 4/5mM brain function is impaired, under 2 can cause coma
Insulin is the only hormone that reduces blood glucose
Meanwhile, glucagon, Catecholamines, Somatotropins, Cortisol all increase it
What organ is in charge of regulating blood glucose? Which cells specifically? In what sort of architecture?
The pancreas if the secretor of insulin and glucagon, main effectors of blood glucose. It is done by cells in ISLETS OF LANGERHANS.
3 cell types coexist there-alpha, beta and gamma
Alpha cells produce glucagon (protein hormone), Beta cells produce Insulin (also protein), and gamma cells Somatostatin
Cells are usually tightly joined by tight junction (impermeable) which creates a small interstitial space in which hormones are secreted and have a very high conc-ensure signalling to other cells to be maximal at all times and change fast. The cells also possess gap junction to communicate with one another
What are the interaction between the different cells of the pancreas?
Insulin-mitotic increase of growth and development, metabolic decrease of blood glucose
Glucagon-decrease blood sugar
Somatostatin-decrease insulin and glucagon production
Explain activators of pancreas B cells, and what its effects are
Many things can increase insulin production-sympathetic and parasympathetic nerves, certain amino acids, certain GI hormones, glucagon and HIGH GLUCOSE
Insulin is inhibited by Somatostatin
The results are
Decreased lipolysis, increased lipogenesis, Increased aa transport and protein synthesis
AND increased Glycolysis, Increase GLUT4 glucose transporter and increased glycogenesis (all leading to lower blood glucose, higher use of it and increase of storage)
Explain activators of pancreas alpha cells, and what its effects are
Increase in glucagon-certain aa, certain GI hormones, Sympathetic and parasympathetic nervous system, LOW GLUCOSE
Decreased by Insulin and somatostatin
Glucagon increases lipolysis (for gluconeogenesis-from the glycerol, and switch to fat use), increase Aa transport to the liver (increased gluconeogenesis), increase hepatic glycogenolysis =>all increase blood glucose
How is insulin synthesised and post translationally modified?
Insulin produced as proinsulin, a chain of aa linked with 3SS bonds and 3 chains -A, C-peptide and B chain
In the VESICLES before secretion, C peptide is cleaved off, leaving “floating” A and B chain linked by SS bonds
Insulin is secreted at a 1:1 ratio to C peptide, so C-pep is a good marker for insulin production
How are glucose levels detected by Beta cells?
The main method is Glucokinase/hexokinase IV-the glucose sensor
B cells have a GLUT2 receptor (not affected by insulin) which always taken up glucose. Glucokinase then catalyses the rate limiting step. But it is readily inhibited at lower levels
At high levels, functions well and starts glycolysis leading to enough energy for Insulin synthesis and release
At normal/low levels, enzyme does not work as well (High Km), and therefore limits glycolysis, and the cell does not have enough energy for Insulin synthesis and release
Furthermore, the ATP produced acts on ATP sensitive K+ channels, letting ions in. This voltage change opens Voltage dependent Ca2+ channels, allowing Ca2+ in
The Calcium is part of the process of releasing insulin vesicles from the cell
Explain the gastrointestinal effects on insulin
Oral vs IV glucose do not have the same effects on insulin production (even at same level)
GI tract produced Glucagon like peptide 1, a gut hormone which inhibits glucagon and increase insulin; it also increases satiety
It is transcribed from the proglucagon gene, by L cells, and have a short half like as degraded by DPPG4
What is first phase insulin release or FPIR?
When taking in glucose, Insulin levels spike , then fall but are maintained lowish as long as glucose is high
That is because a lot of insulin is made in advance, and released when the glucose enters. Then it is continuosly released as the glucose is high (this the second phase release)
List the mitotic and metabolic effects of insulin
Mitotic-Lipoprotein change, smooth muscle hyperthrophy, Ovarian function, Clottin, energy expediture
Metabolic
Glucose: GLUT4 7* increased effect, mostly muscle and adipose tissue. Before sit in vesicle and ready to be recruited, and also decreases Hepatic glucose output (HGO)
protein-Decreases proteolysis
Lipids-Decrease lipolysis, Decrease ketogenesis
FED HORMONE
Describe muscle cells role in gluconeogenesis and different effectors (hormonal)
Muscle cells cannot go gluconeogenesis, but can do proteolysis to produce amino acids/lactate for the liver
Insulin reduces proteolysis, cortisol increases it
Insulin on the other hand increase protein SYNTHESIS, along with Growth hormone
Insulin also reduces O2 expediture by muscle
Explain the role of liver in gluconeogenesis and different hormonal interference
Liver takes up aa, lactate and pyruvate from muscle and other cells-then can convert them to proteins or glucose for the blood
Glucagon increases uptake of aa and use to make glucose (HGO)/ Cats and cortisol als do
Insulin increases protein synthesis and reduces gluconeogenesis
Proteolysis-increased by glucagon
25% of HGO after 10h
What are the 3 main energy stores of the body and how long do they last approx.
Glycogen is short term-16h max. Protein can last for 15 days. Fat lasts for 30-40 days, but cannot be used to make glucose (except glycerol)-used to reduce glucose expenditure by tissues
Describe Adipocyte uptake of FA in relation to hormones, and the place of adipocytes in circulation
After a meal, high LDL/chylo in blood -insulin increased Lipoprotein lipase activity and uptake of FA. Also increases glucose uptake to make glycerol
The 2 are pooled to make non esterified FA, and TAG
These fats are released under action of Cats, cortisol and GH into glycerol and NEFA
lower stomach adipocytes (near liver)/gut are on a different cardiovascular system-gut blood goes by liver before going to heart-and those adipocytes too then
This means important role in storing most of the food, and react more to insulin and stuff
What are ketone bodies, how are they made and regulated
brain needs energy and if glucose goes low, then need to replace-ketone bodies
NEFA come to liver and turned into acyl COA and AcCOA (reduced by insulin, increased by Glcg)
AcCOA makes Acetoacetate then acetone and 3 hydroxybutarate (ketone) then sent to brain
