Week 2 - Function of The Pancreas and Type 1 Diabetes Flashcards
Explain the process of glucose metabolism
- Glucose is a monosaccharide (formed via digestion of starch (polysach.) or lactose from food)
- Glucose is absorbed from small intestine lumen to enterocyte via co-transport with Na (GLUT1)
- Glucose enters blood via transporter called GLUT2)
GLUT = GLUcose Transporter
KEY INFO
2 Important Hormones (both secreted by pancreas)
1. Insulin - ↓ blood glucose conc.
2. Glucagon - ↑ blood glucose conc.
- stimulates gluconeogenesis (formation of new glucose from a.acids and lipids)
- stimulates glycogenolysis (glycogen breakdown)
synthesis = -esis
breakdown = -olysis
No insulin production leads to hyperglycaemia (high blood glucose)
What is the cause of type 1 diabetes
- ABSOLUTE INSULIN DEFICIENCY (casused by autoimmune destruction of insulin producing b-cells in pancreas)
RISK FACTORS:
- Genetics (if parent or sibling has it, ↑ risk if twin has it)
- Envrionmental (diet, vit. D exposure, obesity, viruses)
- People with type 1 can die within days / weeks without insulin replacement
- Type 1 incidence is lower than type 2, commonly presents in children / young people can present later
- type 1 isn’t as common
How do you diagnose type 1 diabetes
- Polyuria (↑ frequency to urinate)
- Abnoramal thirst
- Unexplained weight loss
- Serum glucose levels within diabetic range (5.6 to 11.1)
- > 7 mmol/l (fasting)
- ≥ 11.1 mmol/l (when taken randomly or 2 hrs after glucose tolerance test)
Glucose Tolerance Test - fast overnight, ingest glucose drink in morning + take glucose levels
CAN”T use URINE DIPSTICK test to diagnose as when glucose conc. exceeds renal threshold will appear in urine (glycosuria = everyone can get this not just diabetics
What are the 3 microvascular complications of type 1 diabetes
Small blood vessel damage
- Nephropathy
- diabetic kidney disease; due to damage to small blood vessels in kidney (compromised filtration = protein in urine) - Retinopathy
- caused by damage to small blood vesels in retina
- leads to loss of vision - Neuropathy
- damage to nerves due to hyperglycaemia, decreased blood flow to nerves (these damage small blood vessels)
- diabetic foot problems (can lead to ulceration, amputaiton)
- autonimc neuropathy
What are the macrovascular complications of type 1 diabetes
damage to large blood vessels due to hyperglycaemia
- Athersclerosis in coronary arteries = ↑ CVD risk
- released insulin induces lipase (breaksdown fats for reabsoprtionn into fat cells ~ converted to triglyc. + stored)
- no insulin = fat accumulates in circulation = deposit in aterial walls
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What are the metabolic complications of type 1 diabetes
- Diabetic Ketoacidosis (DKA)
- CAUSE: Insulin deficiency
- INDICATION: high blood glucose >11 + presence of ketones + blood is acidic (when tested)
- enhances hepatic glycogenolysis (glycogen broken down in liver) + gluconeogenesis
- accumulation of ketones causes metabolic acidosis (ketones have low pH) - Hyperosmolar Non-Ketotic Hyperglycaemia (HNKH)
- INDICATION: high blod glucose (BG) + dehdrated + no ketones
- blood glucose is VERY HIGH (>40 mmol/l) - Hypoglycaemia
- CAUSE: adverse effect (low BG) of insulin treatement
- SYMPTOMS: convulsions, inability to swallow, coma, loss of consciousness
ketones = waste product produced when proteins, f.acids, a.acids etc. are used to make glucose
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What are the other complications of type 1 diabetes
Increased risk of
- thyroid disease
- anaemia
- coeliac disease
- reduced life expectancy
- infection
What 2 hormones (incretins) stimulate insulin production
both are peptides
Incretins trigger b-cells (in islet of langerhans) in pancreas to stimulate insulin production
Both incretins found in S.intestines
Both are DEGRADED quickly by DPP4 when released
- GIP (Gastric Inhibitory Peptide)
- syntehsised + relased (from K cells) in response to nutrietnts
- GIP binds to GIPR (GIP receptor) on pancreatic b-cells = ↑ intracellular Ca2+ = insulin secretion
- As Ca2+ binds to vesicles (containing insulin), vesicles fuse with membrane + release insulin
- GLP-1 (Glucagon Like Peptide 1)
- syntehsised + released from L cells
- GLP-1 binds to GLP-1R on pancreatic b-cells = ↑ Ca2+ = insulin secretion
- GLP-1 protects b-cells from apoptosis + stimulates b-cell proliferation
- inhibits glucagon secretion
- slows down rate of glucose production
What causes the release of insulin
Food or Incretins (digestive system hormones produced in S.Intetsines)
- Normal conditions / before glucose K+ ions flow out of cell
- Eat food → causes blood glucose to levels to rise
- glucose spike is called post prandial spike - Increase glucose causes conc. gradient = glucose diffuses (FD) into cell via co-transporters (GLUT)
- As glucose moves in, its respired = ATP produced
- ATP binds to K+ channels = K+ close
- Buildup of K+ ions in cell causes Ca2+ channels to open and Ca2+ enters cell
- Ca2+ binds to vesicles (containing insulin) causing them tof fuse with cell membrane = insulin released
- Increases causes insulin release
- insulin secreted from beta cells in the islet of langerhans (in the pancreas) - Insulin causes ↓ in blood glucose conc
What are the 4 ways insulin decreases blood glucose conc.
- ↑ glucose uptake (into muscle + fat)
- by inserting more glucose channels into cell surface membrane - ↑ glycogen synthesis (glycogenesis in liver)
- ↓ glycogen breakdown (glycogenolysis)
- ↓ gluconeogensis (production of new glucose)
How Is Insulin Biosynthesised
- Starts as a precursor ~ preproinuslin in rough endoplasmic reticulum
- Preproinsulin undergoes proteolytic cleavage to proinsulin
- Then cleavage to insulin + a fragment of uncertain function called C-peptide
If have absolute insulin deficiency = wont see much C-peptide as not much preproinsulin has been broken down
What are the 5 different types of insulin available
- Rapid acting (quickets onset)
- Short acting
- Intermediate acting
- Long acting (BASAL DOSE = everyone needs this)
- Premixed
- Most patients use MULTIPLE INJECTION THERAPY
- felxible for people with irregular lifestyle
- given a long acting insulin + short acting OR rapid before meal - Insulin injections (pens or vials) or pumps
- pre-filled pens, reusable pens, vials
- syringes measure 100 units/ml
- pumps lasts 4-8 years
- pumps used for those who can’t achieve target HbA1c + have hypos (hypoglycaemia) OR HbA1c remains high
How does rapid acting insulin work
- QUICK onset = 5-15 minutes
- Inject immediately / 5 min. before eating or up to 15 min. after
- DURATION: 4 hours
- Good choice for younger people
- Have fewer hypoglycaemic events
- Used combined with other long or immediate acting
How does short acting insulin work
- Onset 30-45 minutes
- Inject at least 30 min. before eating
- DURATION: 5 to 8 hours
- Good for older people / those who have routine
- Used combined with other long or immediate acting
