GLUCOSE HOMOESTASISRegulation of blood glucose levels

DR ROHINI C SANE

PROFESSOR

DEPARTMENT OF BIOCHEMISTRY

DR D Y PATIL MEDICAL COLLEGE

EBENE

Normal values of serum glucose & clinical significance

• Status Physiological levels Diabetes Mellitus

FASTING ˂ 110 MG/DL(˂ 6.1 mmol/lt)

˃ 126 mg/dl (˃ 7 mmols/lt)

1 hr (peak ) after glucose intake

˂ 160 MG/DL(˂ 9.0 mmol/lt)

Not described

2hrs (after glucose ) ˂ 140 MG/DL(˂ 6.1 mmol/lt)

˃ 200 mg/dl (˃11.1 mmols/lt)

Hypoglycemia

• Blood glucose < 45 mg/dl----life threatening ---unconscious ---irreversible brain damage --death

Symptoms

• Head ache

• Anxiety

• Confusion

• Sweating

• Slurred speech

• Seizures

• Coma

• Death

HypoglycemiaCauses

• Insulin over dose (intensive regimes )

• Post pandrial -increase insulin-- >transient hypoglycemia-->mild symptoms

• Pancreatic beta cell tumor-insulin secreting tumor (liver cell dmage—>Hepatocellular damage)

• Alcohol treatment

• hypo secretion of adrenal /pituitary /thyroid hormones

• Drug /dyes induced liver damage

Oxidative pathways of glucose –decreasing glucose levels

• Normal fasting blood glucose ---70-110mg%(4.5—5.5mg%)

• Glycolysis

• HMP shunt

• Uronic acid pathway

Synthetic pathways of glucose –Decreasing glucose levels

• fructose ,Galactose, lactose ,maltose ,sucrose &mucopolysaccharidessynthesis

• Glycogenesis

• Lipogenesis

• Synthesis of non essential amino acids

Sources of glucose in human body

• Absorption of Dietary carbohydrates in GIT (starch /sucrose /glucose/Fructose/ lactose /maltose)

• Gluconeogenesis (amino acids /glycerol /propionate/lactate/pyruvate )

• Glycogenolysis in liver & muscles

Depletion of glucose in human body

• Glycolysis—TCA (for energy purpose)

• GLYCOGENESIS

• SYNTHESIS OF AMINO SUGARS /MONOSACCHARIDES

• SYNTHESIS OF FAT

• HMP SHUNT

• RENAL EXCRETION---RENAL THRESHHOLD ---180MG%

• RENAL TUBULAR MAXIMA FOR GLUCOSE---(TMG)---360 MG%

GLUCOSE HOMEOSTASIS• DEFINITION ---REGULATION OF BLOOD GLUCOSE IN NORMAL RANGE

• NORMAL FASTING BOOD GLUCOSE LEVELS (70—110MG/DL) NORMAL POST PANDRIAL BOOD GLUCOSE LEVELS (110—180MG/DL)

GLUCOSE HOMEOSTASISTWO MECHNISMS OF REGULATION OF BLOOD GLUCOSE

• I HORMONAL REGULATION

HYPERGLYCEMIC HORMONES (MANY )

ONLY HYPOGLYCEMIC HORMONE---- INSULIN

• II ALIMENTARY MECHANISM

Role of stomatch

Role of liver

Role of muscles

Role of kidey

I HORMONAL REGULATION- HYPOGLYCEMIC HORMONE---INSULININCREASES UTILIZATION OF GLUCOSE THROUGH

GLUCOSE UPTAKE

GLYCOLYSIS

GLYCOGENESIS

HMP SHUNT

LIPID SYNTHESIS

DECREASES SYNTHESIS OF GLUCOSE VIA

• GLUCONEOGENESIS

• GLYCOGENOLYSIS

• TREATMENT OF DM ---TOLBUTAMIDE INDUCES INSULIN SECRETION BY BETA PANCREATIC CELLS

I HORMONAL REGULATIONHYPERGLYCEMIC HORMONES(Anti- insulin hormones )

• GLUCAGON(ALPHA cells of islets of langerhans )

• EPINEPHRINE (Adrenal medulla ---under stress conditions )

• THYROXINE (thyroid gland)

• GLUCOCORTICOIDES (adrenal cortex )

• GROWTH HORMONES

• ACTH

I HORMONAL REGULATION- HYPERGLYCEMIC HORMONES

INCREASE GLUCOSE LEVELS BY ENHANCING• GLUCONEOGENESIS• GLYCOGENOLYSIS• ALIMENTARTY ABSORPTION DECREASES UTILIZATION OF GLUCOSE BY DECREASINGGLUCOSE UPTAKEGLYCOLYSISGLYCOGENESISHMP SHUNTLIPID SYNTHESIS

REGULATION OF BLOOD GLUCOSE LEVELS

EFFICIENT

• TO MAINTAIN CONTINUOUS SUPPLY TO BRAIN WHICH HAS OBLIGATORY REQUIREMENT FOR GLUCOSE

• RBC ,RENAL MEDULLA OR CELLS LACKING MITOCHONDRIA NEEDS GLUCOSE AS ENERGY SOURCE

• WELL FED CONDITION –BLOOD GLUCOSE LEVELS HIGH ---INSULIN INCREASES & HYPER GLYCEMIC HORMONES DECREASE (I/G INCREASES)

• STARVATION--- BLOOD GLUCOSE LEVELS LOW-- INSULIN DECREASES & HYPERVGLYCEMIC HORMONES INCREASE IN CIRCULATION (I/GDECREASES)

I ALIMENTARY MECHANISM-STOMATCH

HIGH GLUCOSE LEVELS - WELL FED LOW GLUCOSE LEVELS -STARVATION

DISTENTION OF STOMATCH

SLOW EMPTYING

SLOW ABSORPTION IN GIT

INCREASED ABSORPTION IN GIT

II ALIMENTARY MECHANISM-LIVERHIGH GLUCOSE LEVELS - WELL FED LOW GLUCOSE LEVELS -STARVATION

UTILIZATION OF GLUCOSE INCREASESGLYCOGEN SYNTHESIS INCREASES

GLYCOGENOLYSIS DECREASES

LIPOGENESIS INCREASES

GLUCONEOGENES INCREASES

GLYCOGENOLYSIS INCREASES

GLUCOSE UTILIZATION DECREASE

LACTIC /CORI CYCLE (CONVERSION OF LACTOSE TO PYRUVATE--GLUCOSE INCREASES)

III ALIMENTARY MECHANISM-MUSCLES HIGH GLUCOSE LEVELS- WELL FED LOW GLUCOSE LEVELS STARVATION

UTILIZATION OF GLUCOSE INCREASESGLYCOGEN SYNTHESIS INCREASES

GLYCOGENOLYSIS DECREASES

LLIPOGENESIS INCREASES

GLYCOGENOLYSIS INCREASES

GLUCOSE UTILIZATION DECREASE

IV ALIMENTARY MECHANISM-KIDNEY

HIGH GLUCOSE LEVELS - WELL FED LOW GLUCOSE LEVELS-STARVATION

HYPERGLYCEMIA ---GLYCOSURIA COMPLETE REABSORPTION OF GLUCOSE BY RENAL TUBULAR CELLS

RENAL THRESHOLD –180 MG/DL TMG -360 MG/DL

HIGH GLUCOSE LEVELS- WELL FED LOW GLUCOSE LEVELS -STARVATION