Glucose, Addiction, and Rhythms

17 important questions on Glucose, Addiction, and Rhythms

Where is the maser biological clock located?

The hypothalamus is responsible for the biological clock. It is located in the hypthalamic suprachiasmatic nucleus (SCN).

If the SCN is removed, all rhytm is lost.

Is the daily rhythm in basal plasma glucose levels dependent on feeding?

No, basal plasma glucose levels do show day/nigh rhythm, but have shown to be independent of feeding activity.

The highest levels of glucose are found at the time of awakening.

What does NMDA and Bicuccilline do?

- NMDA: stimulates neurons (glutamate)
- Bicucilline: blocks GABA action entrance in the PVN. So removes the inhibition of glutamate.
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Will there be an bicucullin effect at night?

No, there is no GABA release to the PVN at night, so there is nothing to block by the GABA-antagonist.

GLU can have effect.

What happens after a SCN lesion?

Bicucullin has no effect because the GABA which is blocked by bicucullin is coming from the SCN.

How does GABA work? What is its effect?

The neurons are continuously stimulated by GLU. However, GABA overrules GLU and has a rhythmic pattern. There is no GABA at night, so the ihibition of GLU is gone. Therefore, the stimulation of GLU is only apparent at night.

How does the PVN stimulate the liver?

Via the sympathetic nerve.

This was shown by cutting the para- and the sympathetic nerve. The sympathetic nerve was shown to be important, because without the bicucullin in PVN there was no increase in glucose.

What is the difference between homeostatic and hedonic?

- Homeostatic: eating to maintain bodily functions
Regulated by hypothalamus
- Hedonic: eating because you want something 
Regulated by striatum

What are the types of glucose sensing neurons?

- Glucose inhibited (GI)
- Glucose excited (GE)

Which brain centers express glucose sensing neurons?

Hypothalamus, striatum & brainstem

What does an glucose-sensing cell need?

1. Glucose transporters (Sodium glucose linked cotransporters)
2. Energy sensing enzymes
3. Transmembrane channels sensitive to changes in energy status

What do NPY/AgRP neurons do?

- Are located in the hypothalamus, in the Arcuate Nucleus (Arc), which is close to the blood brain barrier.
- NPY = Neuropeptide Y
AgRP = Agouti related peptide
- Increase food intake
- Are glucose inhibited (GI) neurons 

What do POMC neurons do?

- POMC = Pro-opiomelanocortin
- alpha MSH is derived from POMC
- Located in hypothalamus, in the Arcuate Nucleus (Arc)
- Decreases food intake
- Are glucose excited (GE) neurons   

How does the melanocortin (MC) system work?

There is competition for the MC4R receptor by AgRP and alpha MSH.
- Md4R shows constitutive activity, thus in suppresses food intake
(when there is no MC4R there is no suppression, resulting in an obese phenotype)
- AgRP inhibits MC4R while alpha MSH stimulates MC4R.

How is dopamine linked to glucose metabolism?

- Dopamine is the key neurotransmitter for reward processes
- Produced in ventral tegmental area and substantia nigra
- 5 receptors: D1, D2, D3, D4, D5

The metabolism of glucose release dopamine, so the breakdown is actually needed for the reward system.
Mice: huge preference flavour conditioned with glucose vs flavour linked to non-metabolized glucose.

* Obese subjects have reduced dopamine binding.

To which brain parts has the ARC projections to?

PVN, LH and VMH

LH: 'hunger center
VHM: saturation center

How is the nucleus accumbens (NAc) involved in glucose metabolism?

NAc is involved in rating how much we like a certain food (hedonic value) and also how much we want that food (motivation). It also contains glucose sensing neurons, and when stimulated, blood glucose levels rise.

Dopamine system within NAc!

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