Diabetes Flashcards
What % of DM diagnoses are type 2?
85%
Name 3 places the body can get glucose from
Diet
Breakdown of glycogen stores (glycogenolysis)
Formation of glucose (gluconeogenesis)
Is glucose hydrophilic or hydrophobic?
What does this mean about transport into cells?
Hydrophilic
Diffuses slowly across lipid cell membrane
Requires specific transport proteins to move into cells
List some differences between GLUT and SGLT transporters
GLUT -
Facilitated diffusion
Not energy dependent
SGLT -
Use sodium to move glucose against concentration gradient
Where are the two types of SGLT transporters found?
SGLT-1
Intestines
SGLT-2
Kidneys
Which GLUT transporter is insulin dependent?
Where is it mainly found?
GLUT-4
Fat and muscle
Describe gluconeogenesis
Production of glucose from molecules that aren’t carbohydrates.
Substrates:
Lactate (non-oxidative metabolism, Kreb’s cycle)
Glycerol (fats)
Glutamine and alanine (protein)
Occurs in liver and kidneys
Describe glycogen and glycogenolysis
Multi branched polysaccharide of glucose, storage molecule of glucose
Stored in liver and muscle cells
Describe insulin
51 amino acids peptide hormone
2 protein chains (alpha and beta) linked by disulphide bonds
Where is insulin produced?
B-cells of Islets of Langerhans in the pancreas
Where is glucagon produced?
a-cells of Islets of Langerhans in the pancreas
Where is somatostatin produced?
What is its role?
gamma-cells
Strong inhibitor of insulin and glucagon
Describe biphasic insulin secretion
First phase - rapid onset, lasts 10 minutes
Second phase - prolonged plateau lasting as long as hyperglycaemia persists
Why is it presumed insulin levels are regulated by release rather than synthesis?
Only a portion of stored insulin is released even under maximal stimulation
Name 6 major actions of insulin
Release of GLUT-4 from storage vesicles to cell walls
Inhibit gluconeogenesis
Glycogen synthesis
Promotes protein synthesis
Promotes lipogenesis
Suppress ketogenesis
What can increase the levels of glucagon?
Fasting
Exercise
Stresses e.g. trauma, infection
List 5 major actions of glucagon
Stimulates gluconeogenesis
Stimulates glycogenolysis
Promotes proteolysis
Stimulates lipolysis
Promotes ketogenesis
What do L-cells of the small intestine produce?
Glucagon-like peptides (GLP)
Gastric inhibitory peptide (GIP)
Where is GLP and GIP made?
L cells of the small intestine
What stimulates the release of GLP and GIP?
Oral glucose loading
IV glucose has less of a response
How does adrenaline affect insulin and glucagon release?
Adrenaline inhibits insulin and promotes glucagon secretion
How does the autonomic nervous system affect insulin and glucagon release?
Sympathetic neurons - release noradrenaline - stimulates glucagon + inhibits insulin
Parasympathetic neurons - stimulate insulin, inhibit glucagon
How is cortisol related to insulin?
Cortisol directly inhibits insulin secretion
Cortisol and growth hormone promote _____ and inhibit ______
Promote gluconeogenesis
Inhibit glucose transport
Define diabetes mellitus
A heterogeneous complex metabolic disorder characterised by elevated blood glucose concentration secondary to either resistance to the action of insulin, insufficient insulin secretion, or both
What are the four classifications on the WHO spectrum of disorders of glucose metabolism
Normal
Impaired fasting glycaemia
Impaired glucose tolerance
Diabetes
How is type 1 diabetes classified?`
Autoimmune disease with selective destruction of β-cells resulting in complete insulin deficiency
Can only be treated with insulin
Who normally suffers from type 1 diabetes?
Younger, leaner patients
5-10% of all diabetes cases
Can be associated with other immune diseases e.g. thyroid disorders, coeliac disease
Name four symptoms of type 1 diabetes
Polyuria
Polydipsia
Weight loss
Hyperglycaemia
Why do diabetics have polyuria?
Hyperglycaemia results in glycosuria - exceeds renal capacity to reabsorb
Glucose in urine inhibits concentrating ability of kidney
Water is moved down a concentration gradient with glucose resulting in polyuria
Why do diabetics have polydipsia
Polyuria due to hyperglycaemia, water needs replacing to maintain fluid balance
Hyperglycaemia also directly stimulates thirst response
Why do diabetics experience weight loss?
Unopposed lipolysis and proteolysis (no insulin to appose these systems)
The results of these form gluconeogenesis precursors
What is diabetic ketoacidosis?
When high levels of ketones are produced as an alternative energy source due to lack of glucose absorption into cells due to lack/insensitivity to insulin
Give 3 symptoms of DKA
Shock (dehydration)
High respiratory rate
Abdominal pain
Define type 2 diabetes mellitus
Heterogeneous condition
Characterised by insulin resistance and hyperinsulinemia
Loss of first phase of insulin response
B-cell exhaustion can occur
What other symptoms are usually present with T2DM?
Central/visceral obesity
Dyslipidaemia
Cardiac factors (HTN)
How does Metformin work?
Decreases hepatic gluconeogenesis
What is first line treatment for T2DM?
Diet, exercise and lifestyle measures
List the three broad categories of complications from diabetes
Hypoglycaemia
Microvascular
Macrovascular
Name 3 microvascular complications of diabetes
Nephropathy
Retinopathy
Neuropathy
Name 3 macrovascular complications of diabetes
IHD
Cerebrovascular disease (CVD)
Peripheral vascular disease
Which type of glucose transporter is found on B-islet cells?
GLUT 2
Where are SGLT1 and SGLT2 transporters found?
SGLT1 - intestines (absorption from food)
SGLT2 - kidneys (reabsorption)
1 intestine, 2 kidneys
What is lipolysis?
The breakdown of fats and other lipids by hydrolysis to release fatty acids
What affect does insulin have on glucose production, glucose utilisation, and lipolysis?
Glucose production - DECREASES
Glucose utilisation - INCREASES
Lipolysis - DECREASES
What affect does glucagon have on glucose production, glucose utilisation, and lipolysis?
Glucose production - INCREASES
Glucose utilisation - DECREASES
Lipolysis - INCREASES
List/draw the 6 steps to insulin secretion in response to glucose in B-cells in the pancreas
Glucose moves into B-cell via GLUT-2
Glucose is metabolised which increases ATP
ATP-dependent K+ channels close
This leads to membrane depolarisation
This leads to opening of voltage gated Ca2+ channels and influx
this leads to exocytosis of stored insulin vesicles
Why does insulin have different affects on different target cells?
Insulin activates an insulin receptor but then different secondary pathways can be activated
Describe the relationship between insulin and GLUT 4
GLUT 4 is stored in intracellular vesicles
Insulin promotes fusion of vesicles and transporter insertion into cell walls
This facilitates glucose transport into cells
Which enzyme does insulin promote activation of?
Glycogen synthase
- makes glycogen from glucose
What is glucagon secretion regulated by?
Blood glucose levels
Hypoglycaemia increases glucagon secretion
Hyperglycaemia inhibits glucagon secretion
Is the post-absorptive state of glucose catabolic or anabolic?
Post-absorptive state is catabolic
Is the post-prandial (fed) state of glucose catabolic or anabolic?
Post-prandial is anabolic
