Diabetes

Diabetes：glucokinase expresssed in both beta-cells and liver cells, and the proteins they produced are different due to alternative splicing.

Diabetes

• Symptom
  • lack of blood glucose
    • due to the lack of the effect of insulin
      • Type 1
        • failure
        • develop after 16
        • due to the lack or dysfuction of puncreatic beta cells
          • lack is leads by the autoimmune attack
            • only show symptoms when >80% beta cells are destroyed.
      • Type 2
        • failure
          • Pancreatic Beta cells cannot overcome the Insulin Resistence
          • lack of fully functional insulin receptor
            • insulin independent
          • vicious cycle
            • hyperglycemia increases the production of insulin, high insulin basal level insensitizes pancreatic β cells, high insulin level will stimulates food intake, increase of food intake will suppress the synthesis of insulin receptor.
              • The blood glucose will increase with time.
              • diet is good for the disease.
        • develop after 40
          • affects 18% of the population over 65
        • > 90% of all diabetes
        • clinically and genetically heterogeneous
          • mutations
            • alterations in insulin binding α-subunit or tyrosine kinase β-subunit of the insulin receptor.
      • MODY(maturity-onset diabetes of the young)
        • failure
          • Mutation in glucokinase
            • dominant, MODY2 gene, chromosome 7
              • heterogeneity
                • 30 different mutations on MODY2 gene to inactivate the glicokinase
          • glucokinase expresssed in both beta-cells and liver cells, and the proteins they produced are different due to alternative splicing.
            • It is the substitution of hexokinase in glycolysis
              • Hexokinase has much higher Km then glucokinase, therefore it provides a wider range of metabolic sensation
              • oxidative phosphorylation in beta-cells is used as sensor directly.
        • mild hyperglycaemic syndrome generally stable over time.
          • due to mildly reduced insulin secretion rate
        • reduction of mitocondrial activities can also cause similar syndrom
          • this is one possible cause of Type2 diabetes. because reduction of mitocondrial activities comes when people get old.
    • cause cells straving of glucose
      • accelerates
        • Triglyceride hydrolysis
        • fatty acid oxidation
        • gluconeogenesis
        • ketone body formation
          • kidney controls blood pressure by excreting excess H+ into urine.
          • acidic ketone body strans the buffering capacity of the blood and the ultrafiltration activity of kideney.
          • The increase of blood PH will casues the increase in urine volume.
          • massive lost of Na+,K+,pi, and H20 in urine will casue death
      • kidney malfunction, nerve impairment, cardiovascular disease
      • hyperglycaemia
        • casue blindness
          • retinal degradation
          • cataracts
            • glucosylation of lens proteins.
• Mechanism
  • meal increases blood glucose
    • increase of blood glucose stimulates pancreatic beta cells to release insulin.
      • Molecular Mechanism
      • insulin stimulates skeleton muscles and fat cells to uptake and consume the glucose.
        • Molecular Mechanism
    • increase of blood glucose inhibits the release of glucagon.
    • increase of blood glucose inhibits glucogenloylsis and gluconeogenesis.