Endo – Glucose

Master answer

General

• Normal BSL 4-6mmol/L
• Tight BSL control important as:
  • ↓ BSL: disrupt normal function of brain, retina, gonads (obligate glucose users)
  • ↑ BSL: ↑ osmolality, osmotic load on kidneys → diuresis + cellular dehydration, loss of electolytes/ substrate → tissue damage

BSL control via feedback mechanism

• Sensors: pancreatic islets of Langerhans
• Central regulator: lateral (feeding) and ventromedial (satiety) centres of hypothalamus
• Effectors:
  • Behavioural (feeding)
  • Hormonal: insulin vs. glucoagon balance (act on liver, muscle, adipocytes)
  • Renal (excretion)
  • Modulated by: catecholamines, cortisol, thyroid homrones
    • short term regulation: via secretion or inhibition of insulin + glucagon from pancreatic islets
    • long term: neuronal mechanisms (SNS activation) + hormones (cortisol, GH)

Sensors

• Pancreatic beta cells → sense ↑ BSL
  • Secrete insulin in biphasic pattern: initial rapid ↑ → prolonged slow ↑
  • 1^st phase of insulin secretion: ↑ BSL → glucose enters via GLUT2 → converted to pyruvate → enters TCA → generate ATP → inhibit ATP sensitive K channel → ↓ K efflux → depolarisation → open voltage gated Ca²⁺ channels → exocytosis of insulin granules
  • 2^nd phase of insulin secretion: glutamate produced as by-product of TCA → maturation of other insulin granules
• Pancreatic alpha cells → sense ↓ BSL
  • ↑ glucagon release

Effectors

• insulin: secreted in response to ↑ BSL → following effects to ↓ BSL
  • ↑ GLUT4 insertion into cell membrane → ↑ glucose uptake into cells esp. muscle + fat
  • ↑ glycogen synthesis
  • ↑ glucose utilisation + ↑ fat and protein synthesis
  • ↓ glycogenolysis / ↓ gluconeogenesis
• glucagon: secreted in reponse to ↓BSL → following effects to ↑ BSL
  • ↑ glycogenolysis / ↑ gluconeogenesis
  • minimal effect on adipose tissue and muscle
• Adrenaline: stimulated by ↓ BSL, stress
  • Inhibit insulin
  • Liver: ↓ glycogenesis, ↑ glucose release, ↑ KB
  • Fat: ↑ FFA release, ↓ glucose uptake
  • Muscle: ↓ glucose uptake, ↑ FFA metabolism
• Sustained ↓ BSL stimulates GH + cortisol release
  • ↓ glucose utilisation + ↑ fat utilisation → limiting further ↓ BSL
  • ↓ protein synthesis / ↑ aa release / ↑ FFA metabolism
• Neuronal Mechanisms:
  • Hypothalamus directly stimulated by hypoglycaemia → ↑ SYNS activity → adrenaline release → stimulates hepatic glucose release

Kerr 2016

Answer by Kerr