Anorexia, obesity, and diabetes

13 important questions on Anorexia, obesity, and diabetes

What is produced when glucose drops?

When glucose levels drop, glucagon rises and ketone bodies will be produced.

Diabetes mellitus type 1 resembles fasting. What happens?

Degradation of fat and muscle because insulin is not made, so glucagon leads to this action. And ketone production is stimulated. This all happens despite a high level of glucose.

What are the consequences of glucagon release?

  • Mobilisation of proteins/AA in myocytes
  • Mobilisation of FA from adipocytes
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What is so remarkable about patients with diabetes type 1?

  • Their glucose is very high
  • Their ketone body levels are very high
  • Their urea secretion is very high
  • Their insulin levels are really low
  • Their glucagon levels are really high

What is the path to a keto-acidosis death for diabetic patients?

Glucose is not being taken up by the liver so the oxaloacetate level drops and the TCA cycle slows down. At the same time glucose is not being taken up by the adipocytes, leading to a release of free fatty acids. This will cause ketone bodies to form. The blood pH drops and this can result in coma and death.

What is the function of ubiquitin?

Ubiquitin flags a protein for destruction by proteasome. This proces is catalysed by E3-ligases (specific for certain proteins). The proteasome degrades the protein, cleaving peptide bonds (ATP needed).

What is Atrogin-1 (muscle atrophy F-box)?

It is a muscle-specific E3 protein that is induced by TNF-α (up with inflammation) and reduced by IGF-1 (down with age).

Why does the mortality rate increase for people with obesity?

Mainly because of death from CV disease and non-insulin dependent diabetes (type 2).

What is the difference between pre-DM2 and DM2?

Pre-DM2 gives a higher insulin production (to make up for the insensitivity).
DM2 gives no glucose homeostasis, despite (high) insulin.

What is the end state of DM2?

All the β-cells are dead. So no insulin is produced anymore. In the end DM2 can thus become DM1.

What is indicative of long term exposure to hyperglycemia?

HbA1C levels

Can we overrule hormonal regulation?

  • AMP inhibits gluconeogenesis and stimulates glycolysis by promoting glucose transportes (GLUT4) to go to the membrane and take up glucose
  • Drug treatment: metformin stimulates AMP-dependent kinase
    • This treatment is anti-obesity and anti-diabetic. The side effect is that you become more sensitive to insulin to brain gets signals to eat more

What do you know about malonyl-CoA as signaling molecule?

Malonyl-CoA is a signal for the fed state.

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