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Regulation of phosphoenolpyruvate carboxykinase during postnatal development in the rat
Insights
Phosphoenolpyruvate carboxykinase (PEPcK) activity varies by tissue and age in rats. Fasting, hormones, and cold exposure differentially affect PEPcK, with gut mucosa responses resembling brown fat more than liver.
Area of Science:
- Biochemistry
- Physiology
- Developmental Biology
Background:
- Phosphoenolpyruvate carboxykinase (PEPcK) is a key gluconeogenic enzyme.
- PEPcK activity is crucial in metabolic regulation across different tissues.
- Understanding tissue-specific PEPcK regulation is vital for metabolic studies.
Purpose of the Study:
- To investigate the differential regulation of PEPcK activity in rat liver, brown fat, and intestinal mucosa.
- To examine the effects of fasting, hormones (T3, dexamethasone), and cold exposure on PEPcK activity.
- To compare the responses of PEPcK activity in these tissues to various stimuli.
Main Methods:
- Measurement of PEPcK enzyme activity in tissue homogenates.
- Administration of fasting, triiodothyronine (T3), dexamethasone, and cold exposure to rats of different ages.
- In vivo administration of alpha-adrenergic antagonists and agonists.
Main Results:
- Fasting increases hepatic PEPcK activity in young and older rats, but decreases it in brown fat of rats younger than 14 days.
- Triiodothyronine (T3) and dexamethasone elevate hepatic PEPcK but decrease it in brown fat and gut mucosa.
- Cold exposure mimics the effects of T3 and dexamethasone on PEPcK activity.
- Alpha-adrenergic agents and T3 synergistically increase hepatic PEPcK activity.
- In brown fat, antagonists decrease PEPcK activity, while in the gut, both agonists and antagonists inhibit it.
Conclusions:
- PEPcK activity exhibits distinct regulatory patterns in liver, brown fat, and gut mucosa in response to physiological and pharmacological stimuli.
- Gut mucosa PEPcK regulation shares similarities with brown fat but differs from liver.
- These findings highlight the complex, tissue-specific metabolic adaptations during development and stress.
Abstract:
Phosphoenolpyruvate carboxykinase (EC 4.1.1.49) (PEPcK) activity is high in the liver, brown fat, and small intestinal mucosa of suckling rats. Starvation results in a rise in hepatic activity in newborn and older animals, but a fall in brown fat from rats younger than 14 days. At that age, activity rises in all three tissues on fasting. Both triiodothyronine (T3) and dexamethazone depress activity in gut and (as previously reported) in brown fat, but elevate it in liver. Cold exposure also has a similar effect. Both alpha-antagonist and agonist injections result in elevated hepatic activity. T3 given together with these more than doubles the effect of either drug or T3 given alone. In brown fat only antagonists decrease PEPcK activity, whereas in gut both agonists and antagonist have an inhibitory effect. It is concluded that PEPcK activity in the three tissues responds differently to the same stimuli with gut mucosa being more similar to, but not the same as, brown fat than to liver.