BLOOD GLUCOSE REGULATION Flashcards
NORMAL BLOOD GLUCOSE LEVELS?
4-7.5 mmol/L
SOME HORMONES EXCEPT FOR GLUCAGON HAVE HYPERGLYCEMIC ACTION?
CORTISOL, GROWTH HORMONE, EPINEPHRINE
WHAT IS THE BODY’S LARGEST INSULIN SENSITIVE TISSUE?
SKELETAL MUSCLE
IS UPTAKE OF GLUCOSE BY THE BRAIN INSULIN DEPENDENT? WHY?
NO, IT’S NOT; THE BRAIN WILL TAKE UP GLUCOSE WHATEVER THE INSULIN SOURCES ARE BECAUSE IT IS ITS PRIMARY (ALMOST ONLY) SOURCE OF ENERGY
WHERE IS GLYCOGEN STORED IN THE BODY?
LIVER AND SKELETAL MUSCLE
WHICH GLYCOGEN STORES CAN BE MOBILIZED TO REGULATE BLOOD GLUCOSE DIRECTLY?
LIVER
LIVER GLYCOGEN STORES LAST FOR HOW LONG?
10-12 HRS (AN OVERNIGHT FAST)
EXAMPLES OF INSULIN ACTIONS BEYOND GLUCOSE REGULATION?
- STIMULATES PROTEIN SYNTHESIS
- FACILITATES VASODILATION
- STIMULATES K+ UPTAKE INTO CELLS
- STIMULATES Na+ REABSOPRTION IN RENAL TUBE
ACTIVATES LIPOGENESIS - INHIBITS FATTY ACID OXIDATION
- ACTS AS A GROWTH FACTOR AND HAS EFFECTS ON GENE EXPRESSION
- STIMULATES GLYCOGEN SYNTHESIS
DURING FASTING (EVEN JUST AN OVERNIGHT FAST) THE BRAIN CAN USE WHAT AS A SOURCE OF ENERGY INSTEAD OF GLUCOSE?
KETONE BODIES
HOW AND WHERE ARE KETONE BODIES FORMED?
IN THE LIVER THROUGH OXIDATION OF FATTY ACIDS WHICH ARE RELEASED FROM THE ADIPOSE TISSUE
IF THE BLOOD GLUCOSE LEVELS FALL BELOW WHICH POINT THE SIDE EFFECTS ARE CONVULSIONS, COMA AND DETAH?
1.5 mmol/L
COGNITIVE DYSFUNCTION (INCOORDINATION, ATYPICAL BEHAVIOUR, SPEECH DIFFICULTIES) START OCCURRING IF THE BLOOD LEVELS OF GLUCOSE FALL BELOW:
2.8 mmol/L
POSSIBLE CAUSES OF HYPOGLYCAEMIA?
- EXERTION/EXERCISE
- FASTING
- EXCESS EXOGENOUS INSULIN
- INSULINOMA
- ALCOHOL INTAKE (CAUSES INCREASE IN ENDOCRINE PANCREATIC MICROCIRCULATION, INCREASING INSULIN SECRETION + INHIBITS HEPATIC GLUCONEOGENESIS)
HOW DOES ALCOHOL INFLUENCE GLUCOSE LEVELS?
IT CAUSES INCREASE IN ENDOCRINE PANCREATIC MICROCIRCULATION, INCREASING INSULIN SECRETION + INHIBITS HEPATIC GLUCONEOGENESIS
5 MAIN COUNTER REGULATORY HORMONES TO INSULIN?
GLUCAGON, ADRENALINE, CORTISOL, GROWTH HORMONE, VASOPRESSIN
POSSIBLE CAUSES OF HYPERGLYCAEMIA?
STRESS (CHRONICALLY HIGH CORTISOL AND ADRENALINE)
INABILITY OF INSULIN TO INHIBIT GLUCONEOGENESIS
ABSOLUTE DEFICIENCY OF INSULIN (T1D; AUTOIMMUNE DESTRUCTION OF PANCREATIC BETA CELLS)
RELATIVE INSUFFICIENCY OF INSULIN (INSULIN RESISTANCE OF TISSUES)
WHAT IS INSULINOMA?
BENIGN TUMOUR CAUSING EXCESS ENDOGENOUS INSULIN
COMPLICATIONS ARISING FROM CHRONIC HYPERGLYCAEMIA (E.G. POORLY CONTROLLED DIABETES)?
- THE PROTEINS IN THE BLOOD GET CHEMICALLY MODIFIED BY THE HIGH GLUCOSE CONCENTRATIONS (ONE OF THEM IS HEAMOGLOBIN)
- SORBITOL PATHWAY IS OVER ACTIVE; SORBITOL IS A MONOSACCHARIDE AND IT AND THE FRUCTOSE FORMED FROM IT ARE OSMOTICALLY ACTIVE AND MAY DEPOSIT (ESP SEVERE IN THE LENS OF THE EYE)
- IMPAIRED VASODILATATION (DECREASE IN NITRIC OXIDE FORMATION)
- IMPAIRED REGULATION OF THE BLOOD FLOW TO THE EXTREMITIES + IMPAIRED NERVE FUNCTION RESULTING IN PERIPHERAL NEUROPATHY
WHAT ARE THE RESULTS OF INCREASED SORBITOL SYNTHESIS IN HYPERGLYCAEMIA?
- THE REDOX STATE INSIDE THE CELL IS DYSREGULATED (INCREASE IN THE FORMATION OF REACTIVE OXYGEN SPECIES WHICH ARE DELETERIOUS TO CELL FUNCTION
- SORBITOL AND FRUCTOSE FORMED FROM IT CAN DEPOSIT, ESP IN THE LENS OF THE EYE
WHAT HAPPENS WHEN THE ADIPOSE TISSUE BECOMES INSULIN RESISTANT?
THE LOSS OF ANTI-LYPOLITIC (INHIBITION OF TRIGLYCERIDE BREAKDOWN) EFFECTS OF INSULIN RESULTS IN THE INCREASED RELEASE OF FATTY ACIDS FROM ADIPOSE TISSUES + THE LIVER WILL CONTINUE TO SYNTHESISE AND SECRETE TRIGLYCERIDES WHICH FURTHER CONTRIBUTES TO HYPERLIPIDAEMIA
WHAT IS EUGLYCAEMIA?
A NORMAL LEVEL OF SUGAR IN THE BLOOD
WHAT ARE INCRETINS? + EXAMPLES
PEPTIDES SECRETED BY THE GUT DURING MEALS WHICH PROMOTE GLUCOSE-INDUCED INSULIN SECRETION
- THEY HAVE EFFECTS ON OTHER TISSUES EXCEPT FROM PANCREAS AND THEIR EFFECTS THERE ARE COMPLEMENTARY TO THE EFFECTS OF INSULIN ITSELF
CCK (CHOLECYSTOKININ), GLP-1 (GLUCAGON-LIKE PEPTIDE 1) AND GIP (GASTRIC INHIBITORY PEPTIDE)
WHAT ARE GLIPTINS?
CLASS OF DRUGS, GLP 1 RECEPTOR AGONISTS (ACTIVATE IT)
WHICH CHANGES OCCUR IN PANCREATIC FUNCTIONING AFTER A PROLONGED PERIOD OF INSULIN RESISTANCE?
PANCREAS STARTS SECRETING LESS INSULIN AND INCREASING THE GLUCAGON SECRETION + THE EFFECT OF INCRETINS ON THE BETA CELLS DECREASES
PHYSIOLOGICALLY WHEN DOES THE DIAGNOSIS OF T2DM OCCUR?
INITIALLY WHEN BLOOD GLUCOSE LEVELS ARE HIGH PANCREAS KEEPS PRODUCING MORE AND MORE INSULIN BUT EVENTUALLY THE HYPERGLYCAEMIC AND HYPERLIPIDAEMIC PROFILE OF THE BLOOD RESULTS IN GLUCOLIPOTOXICITY OF BETA CELLS AND THEY LOSE THE ABILITY TO SECRETE INSULIN RESULTING IN DEVELOPMENT OF SEVERE HYPERGLYCAEMIA WHICH LEADS TO T2DM DIAGNOSIS
WHAT ARE SOME STRATEGIES FOR IMPROVING INSULIN SENSITIVITY?
EXERCISE, IMPROVED DIET, WEIGHT CONTROL, INSULIN SENSITIZERS
EXERCISE/MUSCLE CONTRACTION ACTIVATES WHICH GLUCOSE TRANSPORTER?
GLUT 4
WHAT IS THE FIRST LINE MEDICATION FOR INHIBITING HEPATIC GLUCOSE PRODUCTION BY INCREASING ITS INSULIN SENSITIVITY?
METFORMIN
WHAT IS THE DIFFERENCE BETWEEN HIGH AFFINITY AND LOW AFFINITY GLUCOSE TRANSPORTERS?
HIGH AFFINITY TRANSPORTERS WILL ALWAYS BE WORKING AT FULL CAPACITY AT NORMAL PHYSIOLOGICAL BLOOD GLUCOSE CONCENTRATIONS WHILE LOW.AFFINITY TRANSPORTERS HAVE A RATE THAT VARIES ALMOST LINEARLY WITH CHANGES IN PHYSIOLOGICAL BLOOD GLUCOSE LEVELS
DOES FACILITATED DIFFUSION FOR GLUCOSE TRANSPORT IN AND OUT OF CELLS USE ATP?
NO
SGLTs ARE:
SODIUM DEPENDENT GLUCOSE TRANSPORTERS (CO TRANSPORTERS WITH A REQUIREMENT OF SODIUM IONS), WHICH ARE PUMPS AND A TYPE OF SECONDARY ACTIVE TRANSPORT
WHICH ORGAN ARE BOTH SGLTs IMPORTANT IN?
IN KIDNEY
WHICH OUT OF THE 2 SGLTs HAS A HIGHER AFFINITY FOR GLUCOSE?
SGLT 1
WHICH GLUT HAS THE HIGHEST GLUCOSE AFFINITY (LOWEST Km)?
GLUT 3
WHERE ARE GLUT 1 AND GLUT 3 (ESP) EXPRESSED AND HOW IS THEIR AFFINITY RELATED TO INSULIN?
IN THE BRAIN BECAUSE IT NEEDS GLUCOSE TRANSPORT ALL THE TIME, ACTIVITY ISN’T INSULIN DEPENDENT
WHICH GLUT IS PARTICULARLY PROMINENT IN THE BRAIN?
GLUT 1 (GLUT 3 IN NEURONS)
AFFINITY IS ALSO SOMETIMES REFERRED TO AS..
KINETIC PROPERTIES
WHAT IS THE MAIN GLUT OF ADIPOSE TISSUE?
GLUT 4
SGLTs ARE SECONDARY ACTIVE TRANSPORTERS; WHAT DOES THAT MEAN?
IT MEANS THEY DON’T USE ATP THEMSELVES BUT ARE COUPLED TO ATPASES THAT MAINTAIN ION GRADIENTS NECESSARY FOR THE UPTAKE OF GLUCOSE
WHAT HAPPENS TO GLUCOSE WHEN IT GETS INSIDE CELLS?
GLUCOSE IS PHOSPHORYLATED BY HEXOKINASES (START OF GLYCOLYSIS) WITH CORRESPONDING AFFINITIES TO THOSE OF EXPRESSED GLUTs
ARE BETA CELLS INSULIN SENSITIVE?
YES
TYPES AND FUNCTIONS OF INNERVATION OF BETA CELLS OF THE PANCREAS?
BOTH SYMPATHETIC (INHIBITS INSULIN SECRETION) AND PARAS. (STIMULATES INSULIN SECRETION)
WHICH CELLS OUR ON THE OUTER AND WHICH CELLS ON THE INNER PART OF PANCREATIC ISLETS?
BETA CELLS ON THE INNER AND ALPHA CELLS ON THE OUTER
EFFECTS OF PANCREATIC HORMONES ON EACH OTHER?
GLUCAGON + INSULIN GLUCAGON + SOMATOSTATIN INSULIN - GLUCAGON INSULIN - SOMATOSTATIN SOMATOSTATIN - INSULIN SOMATOSTATIN - GLUCAGON
WHICH GLUT AND WHICH HEXOKINASE ARE REPRESENTED IN BETA CELLS?
GLUT 2 AND HK4
INSULIN SECRETION STOPS IF BLOOD GLUCOSE IS BELOW WHICH LEVEL?
3.5 mmol/L
IF AN INDIVIDUAL IS INSULIN RESISTANT, WHAT HAPPENS TO THEIR GLUCOSE LEVELS AFTER A MEAL?
IT TAKES LONGER TO CLEAR OUT THE GLUCOSE FROM THE CIRCULATION AND THE CONCENTRATION REMAINS HIGHER FOR LONGER
WHAT IS THE BASIS OF ORAL GLUCOSE TOLERANCE TEST?
- AS IT TAKES LONGER TO CLEAR OUT THE GLUCOSE FROM THE CIRCULATION IN INSULIN RESISTANT INDIVIDUALS, 2HRS AFTER INGESTING A GLUCOSE BOLUS, THE PLASMA LEVELS OF GLUCOSE ARE VERY DIFFERENT BETWEEN HEALTHY INDIVIDUALS AND THOSE WHO ARE INSULIN RESISTANT
- 75 g GLUCOSE DOSE, >11 mmol/L INDICATES RESISTANCE
WHAT ARE SOME OF THE TESTS USED IN MONITORING GLUCOSE TOLERANCE?
- RANDOM PLASMA GLUCOSE CONCENTRATION
- GLUCOSE CONC. IN PLASMA OF OVERNIGHT FASTED PATIENT (>7 mmol)
- ORAL GLUCOSE TOLERANCE TEST
- HbA1C MEASUREMENT (>6.5%)
WHICH GLUCOSE PLASMA CONC. AFTER AN OVERNIGHT FAST MIGHT INDICATE INSULIN RESISTANCE?
> 7mmol
WHAT IS THE MAIN FORM OF GLYCATED HEMOGLOBIN?
HbA1C
WHICH LEVELS OF GLYCATED HEMOGLOBIN HbA1C MIGHT INDICATE INSULIN RESISTANCE?
> 6.5%
