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Blood glucose — the negative feedback loop

Both arms of the loop around a 4.0–5.5 mmol L⁻¹ set point: a meal pushing glucose up, β cells releasing insulin and GLUT4 pulling it into muscle and fat, then α cells and glucagon driving glycogenolysis and gluconeogenesis when it falls — with the two ways the loop breaks and the HbA1c threshold that detects them.

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{
  "nodes": [
    { "id": "meal", "type": "funnel", "label": "Meal — carbohydrate digested to glucose", "x": 40, "y": 40, "width": 150, "height": 104, "fill": "#ede9fe", "stroke": "#6d28d9", "bold": true },
    { "id": "rise", "type": "chevron", "label": "Glucose rises above 5.5 mmol L⁻¹", "x": 215, "y": 40, "width": 150, "height": 104, "fill": "#fef3c7", "stroke": "#b45309", "bold": true },
    { "id": "betacells", "type": "sphere", "label": "Pancreatic β cells sense the rise", "x": 390, "y": 40, "width": 150, "height": 104, "fill": "#e0f2fe", "stroke": "#0369a1", "bold": true },
    { "id": "insulin", "type": "syringe", "label": "Insulin into the hepatic portal blood", "x": 565, "y": 40, "width": 150, "height": 104, "fill": "#e0f2fe", "stroke": "#0369a1", "bold": true },
    { "id": "glut4", "type": "gate", "label": "GLUT4 moves to muscle and fat membranes", "x": 740, "y": 40, "width": 150, "height": 104, "fill": "#fef3c7", "stroke": "#b45309", "bold": true },
    { "id": "uptake", "type": "chevron", "label": "Glucose taken up — the level falls back", "x": 915, "y": 40, "width": 150, "height": 104, "fill": "#fce7f3", "stroke": "#be185d", "bold": true },
    { "id": "setpoint", "type": "target", "label": "Set point 4.0 to 5.5 mmol L⁻¹ fasting", "x": 40, "y": 200, "width": 150, "height": 104, "fill": "#ccfbf1", "stroke": "#0f766e", "bold": true },
    { "id": "islets", "type": "gauge-chart", "label": "The islets are receptor and control centre", "x": 215, "y": 200, "width": 150, "height": 104, "fill": "#e0f2fe", "stroke": "#0369a1", "bold": true },
    { "id": "glycogen", "type": "stacked-cylinder", "label": "Liver and muscle glycogen — the buffer", "x": 390, "y": 200, "width": 150, "height": 104, "fill": "#dbeafe", "stroke": "#1d4ed8", "bold": true },
    { "id": "lipogenesis", "type": "sphere", "label": "Surplus stored as fat once glycogen fills", "x": 565, "y": 200, "width": 150, "height": 104, "fill": "#dbeafe", "stroke": "#1d4ed8" },
    { "id": "feedback", "type": "conveyor", "label": "Negative feedback — the effect cancels it", "x": 740, "y": 200, "width": 150, "height": 104, "fill": "#f1f5f9", "stroke": "#475569", "bold": true },
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    { "id": "glycogenolysis", "type": "gear", "label": "Glycogenolysis frees the stored glucose", "x": 390, "y": 360, "width": 150, "height": 104, "fill": "#fef3c7", "stroke": "#b45309", "bold": true },
    { "id": "gluconeogenesis", "type": "conveyor", "label": "Gluconeogenesis from lactate and amino acids", "x": 565, "y": 360, "width": 150, "height": 104, "fill": "#fef3c7", "stroke": "#b45309", "bold": true },
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    { "id": "type1", "type": "cross", "label": "Type 1 — β cells destroyed, no insulin", "x": 40, "y": 520, "width": 150, "height": 104, "fill": "#fee2e2", "stroke": "#b91c1c", "bold": true },
    { "id": "type2", "type": "cross", "label": "Type 2 — the receptors stop responding", "x": 390, "y": 520, "width": 150, "height": 104, "fill": "#fee2e2", "stroke": "#b91c1c", "bold": true },
    { "id": "hba1c", "type": "line-chart", "label": "HbA1c ≥ 48 mmol/mol confirms diabetes", "x": 740, "y": 520, "width": 150, "height": 104, "fill": "#ccfbf1", "stroke": "#0f766e", "bold": true }
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    { "id": "e2", "source": "rise", "target": "betacells", "thickness": 2.5 },
    { "id": "e3", "source": "islets", "target": "betacells", "style": "dashed" },
    { "id": "e4", "source": "setpoint", "target": "islets", "label": "the value being defended", "style": "dashed" },
    { "id": "e5", "source": "betacells", "target": "insulin", "thickness": 2.5 },
    { "id": "e6", "source": "insulin", "target": "glut4", "thickness": 2.5 },
    { "id": "e7", "source": "glut4", "target": "uptake", "thickness": 2.5 },
    { "id": "e8", "source": "insulin", "target": "glycogen", "label": "glycogenesis in liver and muscle", "thickness": 2.5 },
    { "id": "e9", "source": "insulin", "target": "lipogenesis" },
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    { "id": "e14", "source": "alphacells", "target": "glucagon", "thickness": 2.5 },
    { "id": "e15", "source": "glucagon", "target": "glycogenolysis", "thickness": 2.5 },
    { "id": "e16", "source": "glycogen", "target": "glycogenolysis", "label": "draws on the buffer", "style": "dashed" },
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    { "id": "e23", "source": "adrenaline", "target": "release", "label": "glucose up regardless of the set point", "style": "dashed" },
    { "id": "e24", "source": "type1", "target": "betacells", "style": "dashed" },
    { "id": "e25", "source": "type2", "target": "glut4", "label": "insulin is present but ignored", "style": "dashed" },
    { "id": "e26", "source": "hba1c", "target": "type2", "label": "three months of average glucose", "style": "dashed" }
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