Glucose Uptake and Exercise (LOIL 2) Flashcards
what family do the ‘Facilitative Glucose Transporters (GLUTs)’ belong to ?
Solute Carrier Gene Family (SLC2a)
state 4 facts about the GLUT family
- different substrate specificity and affinity for glucose and other sugars
- different functions and tissue distribution
- transport glucose don the concentration gradient (facilitative diffusion)
- bidirectional transport
GLUT2 - a glucose sensing glucose transporter - is found in what 4 locations ?
- pancreatic beta cells
- hepatocytes
- basolateral membrane of the intestine
- kidney proximal tubule
state 3 facts about GLUT2
- a high capacity glucose transporter
- has a low affinity for glucose (Km of approx. 11 mM)
- doesn’t saturate easily, so when there is an abundance of glucose in the blood, it will transport as much glucose as it can inside the cell
state 4 facts about GLUT3
- found predominantly in the neurones / brain
- has a very high affinity for glucose
- brain requires a lot of glucose to survive
- ensures that the brain receives glucose constantly so that it can function properly
what is GLUT4 ?
GLUT4 is a highly specialised glucose transporter regulated by insulin and contraction and is in all insulin sensitive tissue
what its GLUT4’s original name ?
Insulin-Responsive Glucose Transporter (IRGT)
how does GLUT4 work ?
GLUT4 translocates/traffics to the plasma membrane in response to insulin stimulation or muscular contraction
what does GLUT4 have, and what is the effect of this ?
has a specialised intracellular storage component called ‘GLUT4 Storage Component (GSC)’ - from there it is recruited to the plasma membrane
what is the effect of GLUT4 also being stimulated by muscle contraction ?
muscular contraction can also stimulate the translocation / trafficking of GLUT4 to increase glucose uptake during exercise
what is the effect of a defect in GLUT4 trafficking ?
defects in GLUT4 trafficking is an early manifestation of insulin resistance and the pre-diabetic phase of T2D
state an additional fact about GLUT5
GLUT5 is an exclusive transporter present in the gut enterocytes
state 5 expansionary facts to the following heading:
‘regulation of glucose metabolism during exercise’
- glucagon secretion inc^ to promote glycogenolysis
- (nor)epinephrine release further inc^ glycogenolysis
- cortisol inc^ to promote protein catabolism for later gluconeogenesis
- GH inc^ to inc^ FFA oxidation, lipolysis and gluconeogenesis
- insulin secretion dec^ to dec^ glucose storage
state what it is meant by the key term - ‘Glucose-Fatty Acid Cycle’
a homeostatic mechanism to control circulating concentrations of glucose and fatty acids
state what the following mean:
1) LCFA
2) TAG
3) Pyr
1) LGFA = long chain fatty acid
2) TAG = triaglycerol
3) Pyr = pyruvate
explain the mechanism of the ‘inhibition of glucose utilisation by fatty acid oxidation’ (4 points)
- level of inhibition is graded and most severe at the level of pyruvate dehydrogenase (PDH) and less severe at the level of PFK
- PDH inhibition is caused by Acetyl CoA and NADH accumulation resulting from FFA oxidation
- PFK inhibition results from citrate accumulation in the cytosol
- effect = reroute glucose towards glycogen synthesis and pyruvate to anaplerosis and/or gluconeogenesis
explain the mechanism of ‘inhibition of FFA oxidation by glucose’
- mediated by Malonyl CoA, the conc ^ which depends on Acetyl-CoA Carboxylase (ACC) activity, and which inhibits the entry of LCFA into the mitochondria
- effect = reroutes the FFA’s towards esterification
state what it is meant by the key term - esterification
Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product
state what it is meant by the key term - diabetes
a disease in which the body’s ability to produce or respond to the hormone insulin is impaired, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood
state what it is meant by the key term - Type 1 Diabetes
Type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition in which the pancreas produces little or no insulin
state what it is meant by the key term - Type 2 Diabetes
ype 2 diabetes occurs when the body doesn’t produce enough insulin to function properly, or the body’s cells don’t react to insulin
what are the 3 main peripheral organs responsible for lowering the glucose concentration in the blood ?
- skeletal muscle
- adipocytes
- hepatocytes
what is diabetes mainly characterised by ? (2 points)
- hyperglycaemia
2. insulin-resistance state
how many people in the world live with diabetes ?
463 million
how many people died from diabetes in 2007 ?
4 million (1 every 6 seconds)
how much spending was spent on diabetes in the UK in 2019 ?
760 billion (12% of total world spending in adults)
how many children have type 1 diabetes in the UK ?
> 1 million
how many people live in the UK with diabetes and don’t know about it ?
approx. 1 million
state 5 characteristics of Type 1 Diabetes
- insulin dependent - requires insulin to treat
- typically developed as a child or young adult
- autoimmune disease which destroys pancreatic beta cells meaning no insulin is secreted
- represent 10% of diabetes cases
state 4 characteristics about Type 2 Diabetes
- non-insulin dependent diabetes
- represent 90% of cases
- typically effect aged >45 who are also overweight
- begins with insulin resistance, usually ends in the ability to produce insulin
what is ‘Gestational Diabetes’ ?
is detected during pregnancy and is characterised by the inability of the body to respond to the increasing demands of insulin during the latter stages of foetal development
state the 3 forms of rare diabetes
- MODY: Maturity Onset Diabetes of the Young - 1-5 % of all diabetes cases
- Neonatal Diabetes: 1 in 300,000 - 400,000 births
- diabetes related to mitochondrial DNA mutations, or maternally inherited diabetes and deadness (MIDD) - 1% of all cases
state, and explain, the 3 phases of Type 2 Diabetes development
- inc^ BW and obesity but normal blood glucose conc^ (euglycemia) with hyperinsulinemia to compensate for insulin resistance of peripheral organs (pre-diabetes)
- obesity with inc^ insulin resistance of peripheral organs with hyperinsulinemia (non-insulin dependent diabetes)
- established insulin resistance (hyperglycaemia) and gradual dec^ in insulin secretion (hypoinsulinemia) - insulin dependent diabetes
state 2 facts about phase 1 of Type 2 Diabetes
- early diagnosis is key - lifestyle and nutrition interventions in P1 or P2 can put pre-diabetes into remission
- the earliest manifestation of pre-diabetes in the insulin resistance of peripheral tissue and more precisely a deficit in the translocation of GLUT4
summarise, in 2 points, what P1 of T2D diabetes is
- pre-diabetes
2/ obesity, normal glucose levels and compensatory hyperinsulinemia
summarise, in 2 points, what P2 of T2D diabetes is
- non-insulin dependent phase
2. strong insulin resistance with hyperglycaemia, compensator hyperinsulinemia
summarise, in 2 points, what P3 of T2D diabetes is
- insulin-dependent phase
2. hyperglycaemia with insulin resistance, hypoinsulinemia with gradual loss of function to beta pancreatic cells
