INSULIN RESISTANCE AND TYPE 2 DIABETES Flashcards
WHICH CELLS OF THE PANCREAS HAVE AN EXOCRINE FUNCTION AND SECRETE DIGESTIVE ENZYMES?
ACINAR CELLS
WHERE AND HOW ARE PANCREATIC DIGESTIVE ENZYMES TRANSPORTED?
INTO THE DUODENUM, BY THE PANCREATIC DUCT
WHAT PERCENTAGE OF PANCREATIC CELLS ARE INSULIN RELEASING BETA CELLS?
60%
WHAT PERCENTAGE OF PANCREATIC CELLS ARE GLUCAGON RELEASING APLHA CELLS?
30%
WHERE ARE INSULIN, GLUCAGON AND SOMATOSTATIN RELEASED TO AND HOW?
PANCREATIC ISLETS ARE DRAINED BY THE CAPILLARIES, SO THEY ARE SECRETED DIRECTLY INTO THE BLOOD STREAM
WHAT IS THE MAIN GLUT IN THE PANCREAS?
GLUT 2
INSULIN WON’T BE SECRETED IF THE GLUCOSE LEVELS ARE BELOW?
3.5 mmol/L
K+ CONCENTRATION IS USUALLY HIGHER INSIDE OR OUTSIDE THE CELL?
INSIDE
STEPS IN GLUCOSE STIMULATED INSULIN SECRETION BY THE PANCREAS:
- PANCREAS USES GLUCOSE TO PRODUCE ATP VIA GLYCOLYSIS
- ATP WILL CLOSE THE POTASSIUM CHANNELS AT THE CELL MEMBRANE WHICH LEADS TO HYPERPOLARIZATION
- THIS STIMULATES CALCIUM CHANNELS AND THE CALCIUM INDUCES THE RELEASE OF INSULIN-CONTAINING VESICLES (EXOCYTOSIS)
- INSULIN IS THEN SECRETED INTO THE BLOOD STREAM
HOW DO FATTY ACIDS REGULATE INSULIN SECRETION AND WHAT CAN BE RESULTS OF EXCESSIVE FATTY ACID CONSUMPTION RELATED TO INSULIN FUNCTIONING?
- AFTER A MEAL, APART FROM GLUCOSE, WE ALSO HAVE A CERTAIN AMOUNT OF FATTY ACIDS IN OUR SYSTEM
- WHEN VERY HIGH AMOUNTS OF FATTY ACIDS ARE EATEN, THE CLOSING OF K+ AND OPENING OF Ca2+ CHANNELS INDUCED BY THOSE FATTY ACIDS WILL INCREASE THE SECRETION OF INSULIN EVEN FURTHER
- THIS LEADS TO HYPERINSULINEMIA, WHICH WILL LEAD THE BODY TO STATRT DEVELOPING INSULIN RESISTANCE TO AVOID GLUCOSE DISAPPEARING TOO FAST
2 MAIN SUBSTRATES REGULATING INSULIN SECRETION?
GLUCOSE AND FATTY ACIDS
HOW DOES GLUCAGON INFLUENCE INSULIN AND WHY?
GLUCAGON STIMULATES INSULIN TO SOME EXTENT; IT IS LIKE A SAFETY BELT TO MAKE SURE THE BODY DOESN’T USE ALL ITS RESERVES TOO QUICKLY; IF INSULIN IS SECRETED WITH GLUCAGON IT WILL BALANCE ITS EFFECTS
WHAT IS THE MAIN ROLE OF SOMATOSTATIN?
MAKING SURE NEITHER INSULIN OR GLUCAGON ARE SECRETED IN EXCESSIVE AMOUNTS
WHAT DOES INSULIN DO TO GLUCAGON SECRETION?
SUPPRESSES IT
WHAT ARE INCRETINS + ONE EXAMPLE?
HORMONES SECRETED BY THE INTESTINE WHICH ACTIVATE INSULIN SECRETION (REDUCE BLOOD GLUCOSE) AND DECREASE FOOD INTAKE.
STRESS HORMONE (LIKE ADRENALINE AND CORTISOL) WILL ACTIVATE WHICH PANCREATIC ENZYME?
GLUCAGON; INDICATE THAT BODY NEEDS MORE GLUCOSE
HOW MANY PHASES IN INSULIN SECRETION ARE THERE AND WHAT ARE THEY?
2;
- ACUTE RESPONSE TO GLUCOSE WHERE THE INSULIN SPIKES
- SUSTAINED SECRETION INDEPENDENT OF GLUCOSE
HOW MUCH DO THE PHASES OF INSULIN SECRETION LAST AND WHAT ARE THE MAIN GOALS OF EACH PHASE?
1) 10 MINS, GOAL IS TO DRAMATICALLY REDUCE BLOOD GLUCOSE LEVELS AFTER A MEAL
2) 3-4 HRS, SLOW RELEASE, GLUCOSE LEVELS SHOULD BE NORMAL BY THE END OF IT
WHEN DOES THE 2ND PHASE OF INSULIN SECRETION REACH PLATEAU?
AT AROUND 3 HRS
DURING WHICH PHASE OF INSULIN SECRETION DOES INSULIN TURN OFF ALL OTHER PATHWAYS THAT WERE PRODUCING GLUCOSE?
2ND PHASE
WHICH PHASE OF INSULIN SECRETION IS LOST IN INSULIN RESISTANCE AND DIABETES?
1ST
NORMAL GLUCOSE LEVELS IN A FASTED STATE (E.G. AFTER AN OVERNIGHT SLEEP)?
3.9-5.5 mmol/L
WHAT ARE THE NORMAL BLOOD GLUCOSE LEVELS 2 HRS AFTER A MEAL?
<7.8 mmol/L
HbA1C LEVELS SHOULD NOT EXCEED WHAT PERCENTAGE IN HEALTHY INDIVIDUALS?
6%
WHAT IS Hb TURNOVER TIME AND HOW IS THAT HELPFUL IN TERMS OF INTERPRETING SOMEONE’S GLUCOSE LEVELS?
3 MONTHS
A WAY TO KNOW IF GLUCOSE LEVELS HAVE BEEN HIGH FOR A LONG TIME
INSULIN’S 3 MAJOR TARGET TISSUES?
LIVER, MUSCLE AND ADIPOSE TISSUE
TISSUES CONTAINING GLUT 4 ARE ACTIVATED DURING WHICH PHASE OF INSULIN SECRETION?
1ST
WHAT PERCENTAGE OF DIABETES CASES ARE ATTRIBUTABLE TO T2D?
90%
WHAT PERCENTAGE OF DIABETES CASES ARE ATTRIBUTABLE TO T2D?
90%
WHICH TYPE OF DIABETES IS ALSO REFERRED TO AS ‘JUVENILE DIABETES’?
T1D
DIFFERENCES BETWEEN TYPE I AND TYPE II DIABETES?
TYPE I: ONSET USUALLY IN YOUNGER YEARS, SHORT HISTORY, ACUTE ONSET, DESTRUCTION OF BETA CELLS BY THE IMMUNE SYSTEM, PATIENTS USUALLY NOT OVERWEIGHT, INSULIN DEFICIENCY, REQUIRES DAILY INSULIN INJECTIONS FROM DIAGNOSIS, OFTEN RANDOM, ASSOCIATED WITH WEIGHT LOSS, CONSTANT HUNGER AND SOME OTHER T2D SYMPTOMS
TYPE II: APPEARS LATER IN LIFE, INSIDIOUS ONSET, INSULIN RESISTANCE NOT LACK OF SECRETION, PATIENTS OFTEN OVERWEIGHT, LIFESTYLE CHANGES CAN HAVE A REVERSING EFFECT, IF UNTREATED THE PANCREAS CAN GET EXHAUSTED AND DECREASE INSULIN SECRETION SO THE SYMPTOMS START TO RESEMBLE T1D MORE, DRY MOUTH, EXCESSIVE THIRST, FATIGUE, BLURRED VISION
WHAT IS THE GREATEST RISK FACTORS FOR T2D?
OBESITY
MAIN SIMILARITY BETWEEN T1D AND T2D?
IN BOTH CASES CELLS DON’T UPTAKE GLUCOSE FROM THE BLOOD STREAM SO THE PLASMA GLUCOSE LEVELS ARE HIGH
1ST STEP OF IMPAIRED GLUCOSE METABOLISM IS?
INSULIN RESISTANCE
WHAT HAPPENS TO GLUCOSE METABOLISM AND INSULIN SECRETION AFTER INSULIN RESISTANCE DEVELOPS?
- INSULIN SECRETION INITIALLY INCREASES TO COMPENSATE FOR THE RESISTANCE
- AFTER AWHILE THE RATE BECOMES TOO HIGH FOR THE PANCREAS AND THE HIGH AMOUNT OF FAT IS TOXIC FOR BETA CELLS
- THE INSULIN SECRETION STARTS DECLINING BUT THE LEVELS ARE STILL ABOVE NORMAL
- GLUCOSE LEVELS START GETTING HIGHER AFTER THIS
- STATE OF IMPAIRED GLUCOSE TOLERANCE AND CLEARANCE
IF INSULIN RESISTANCE IS SUSPECTED, WHICH TEST ARE PEOPLE ASKED TO DO?
ORAL GLUCOSE TOLERANCE TEST (OGTT)
TISSUES WITH WHICH GLUT MAINLY BECOME INSULIN RESISTANT?
GLUT 4 (MUSCLE AND ADIPOSE TISSUE)
DIABETES IS REALLY DECLARED WHEN GLUCOSE LEVELS ARE SO HIGH THAT WHICH ORGAN PARTICIPATES IN CLEARING THE GLUCOSE AND HOW IS THIS DETECTED?
KIDNEYS, THERE IS GLUCOSE IN THE URINE
WHAT DOES ‘GLUCOSURIA’ MEAN?
PRESENCE OF GLUCOSE IN THE URINE
WHAT IS LIPID SPILL OVER AND WHICH CONDITION CAN CAUSE IT?
LIPID ACCUMULATION IN TISSUES APART FROM ADIPOSE TISSUE
CAN HAPPEN IN TYPE II DIABETES BECAUSE LIPOLYSIS ISN’T SUPPRESSED AND MUSCLES NEED TO USE FATTY ACIDS AS FUEL INSTEAD OF GLUCOSE BECAUSE THEY CAN’T UTILIZE GLUCOSE, AND ALL THIS LEADS TO MASSIVE AMOUNT OF FATTY ACIDS IN THE BLOOD
EXAMPLES OF METABOLIC PATHWAYS IMPAIRED BY DIABETES AND INSULIN RESISTANCE?
INSULIN PROPERTIES LOST SO:
- GLYCOGEN SYNTHESIS ISN’T ACTIVATED SO THE EXCESS GLUCOSE CAN’T BE STORED
- INCREASED PROTEOLYSIS (WASTING)
- MUSCLE USES FATTY ACIDS FOR ENERGY; FATTY ACIDS OXIDATION INCREASED
- LIVER PRODUCES GLUCOSE AT ALL TIMES
- FASTING GLUCOSE LEVELS ARE ALSO INCREASED
ECTOPIC TISSUE MEANING:
GROWTH OF NORMAL TISSUE IN THE INCORRECT ANATOMICAL POSITION
IN INSULIN RESISTANT INDIVIDUALS, THE INCREASED RELEASE OF FATTY ACIDS WILL RESULT IN INCREASED ACETYL CoA PRODUCTION. WHAT WILL THE CONSEQUENCES OF THIS BE ON THE GLYCOLYSIS PATHWAY?
- IT WILL FIRSTLY INHIBIT PYRUVATE HYDROGENASE FROM CONVERTING PYRUVATE INTO MORE ACETYL CoA
- PYRUVATE WILL ACCUMULATE
- THIS WILL SUPPRESS THE 1ST STEP OF GLYCOLYSIS (CATALISED BY HEXOKINASE)
- GLUCOSE WILL THEREFORE NOT BE BROKEN DOWN AND THE LEVELS WILL BE EVEN HIGHER
WHY DO BETA CELLS START DYING IN OBESE INSULIN RESISTANT INDIVIDUALS?
BECAUSE THE CONTINUOUS RELEASE OF FATTY ACIDS LEADS TO CONTINUOUS ACTIVATION OF THE BETA CELLS AND THE PANCREAS CAN’T KEEP UP,
FATTY ACIDS ARE TOXIC TO BETA CELLS!!!!!
FATTY ACIDS INDUCE INFLAMMATION. HOW WILL THIS AFFECT INSULIN FUNCTIONING?
INFLAMMATION WILL LEAD TO PRODUCTION OF MOLECULES (OFTEN CYTOKINES) THAT THEMSELVES DISRUPT THE INSULIN SIGNALLING
GESTATIONAL DIABETES AFFECTS WHAT PERCENTAGE OF PREGNANCIES?
10%
GESTATIONAL DIABETES PREVALENCE IS ESP. HIGH IN WOMEN OF WHICH DESCENT?
BLACK SOUTH AFRICAN WOMEN
AT WHICH STAGE OF PREGNANCY DOES GESTATIONAL DIABETES USUALLY APPEAR?
END OF THE 2ND TRIMESTER
WHICH WOMEN WILL BE GIVEN OGTT TEST WHEN PREGNANT REGARDLESS OF IF THEY HAVE THE SYMPTOMS?
OLDER WOMEN, OBESE WOMEN, WOMEN WITH HISTORY OF T2D…
CHANGES IN INSULIN SECRETION AND GLUCOSE METABOLISM IN ALL PREGNANT WOMEN?
ALL WOMEN DEVELOP INSULIN RESISTANCE WITH HYPERINSULINEAMIA BUT WITH NORMAL GLUCOSE LEVELS SO THE GLUCOSE OF THE MOTHER CAN BE SPARED AND USED FOR THE FETAL DEVELOPMENT
WHAT HAPPENS TO INSULIN PRODUCTION IN GESTATIONAL DIABETES?
BETA CELLS DON’T PRODUCE ENOUGH INSULIN TO COMPENSATE FOR THE NORMAL INSULIN RESISTANCE WHICH LEADS TO HYPERINSULINEMIA WITH HYPERGLYCAEMIA
GESTATIONAL DIABETES IS A DISORDER OF WHICH ORGAN AND HOW?
PLACENTA; LINKED DIRECTLY TO THE GOOD FUNCTIONING OF THE PLACENTA, RESOLVES AFTER DELIVERY
EFFECTS OF GESTATIONAL DIABETES ON INFANTS?
MACROSOMIA, INCREASED RISK OF OBESITY, DIABETES AND OTHER DISORDERS LATER IN LIFE
1ST LINE MANAGEMENT OF T2D?
FOLLOWING DIET AND EXERCISE PLAN
DRUGS FOR INSULIN RESISTANCE MANAGEMENT?
- INSULIN SENSITIZERS
- INCREASED INSULIN SECRETION (GLP1 ANALOGUES)
- REDUCED HEPATIC GLUCOSE PRODUCTION (METFORMIN)
WHAT DOES METFORMIN DO?
REDUCES HEPATIC GLUCOSE PRODUCTION
DPPiV INHIBITORS HAVE TO BE GIVEN WITH WHAT MEDICATION TO AVOID INACTIVATION OF IT?
GLP1 ANALOGUES
WHAT ARE THIAZOLIDINEDIONES (TZD)?
DRUGS WHICH ACT LIKE INSULIN SENSITIZERS; INCREASE INSULIN SENSITIVITY AND DECREASE LYPOLYSIS, BUT LEAD TO INCREASE IN ADIPOSE TISSUE AND INCREASED STROKE RISK SO THEY WERE REMOVED FROM THE MARKET
