Details

Autor(en) / Beteiligte

• Chometton, Sandrine
• Winnicki, Elizabeth
• Schier, Lindsey

Titel

A Role for Glucokinase in the Mediobasal Hypothalamus in Glucose Appetition

Ist Teil von

• Obesity (Silver Spring, Md.), 2022-11, Vol.30, p.173-173

Ort / Verlag

Silver Spring: Blackwell Publishing Ltd

Erscheinungsjahr

2022

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Background: Obesity is related to excess intake of simple sugars. This is widely attributed to their sweet taste, but abundant data show that glucose also rapidly stimulates ingestion from other oral and postoral sites. How this is channeled into brain circuits governing motivation and metabolism remain unclear. Methods: Here, we assessed if consumption of small volumes of sugars (~3.5 ml/kg over 3 min) or volume/kg-matched intragastric (IG) sugar infusion, meant to mimic the early phase of a meal, or intraperitoneal (IP) injection of glucose, engage glucokinase (GCK), a glucosensing intermediary, in the mediobasal hypothalamus (MBH) in fasted male rats. Next, we assessed if streptozotocin (STZ)-induced diabetes (65 mg/kg, IP), which destroys insulin-secreting β cells and reduces arcuate nucleus GCK expression, disrupts within meal glucose appetition. Results: Short term glucose intake upregulated GCK mRNA, but neither intake of isoconcentrated fructose, α-methyl-D-glucopyranoside (non-metabolizable glucose analog, αMDG), nor IG infusions of glucose, fructose, or αMDG had this same effect. Moreover, oral consumption of a low-calorie sweetener (0.1% saccharin) combined with IG glucose, fructose, or saline was not sufficient to boost MBH GCK under similar conditions. Systemic injection of low (0.5 g/kg, IP) and high (1 g/kg, IP) glucose also had no effect on MBH GCK expression, compared to IP saline, in fasted male rats. Finally, whereas control rats licked significantly more for glucose than fructose, especially in the early phase of the meal, STZ-treated rats failed to express this rapid stimulation of licking in response to glucose. Conclusions: In conclusion, glucose ingestion appears to be a key determinant of the modulation of GCK expression in the MBH. Ongoing experiments are focused on understanding the link between the cephalic phase insulin release, GCK-linked glucosensors of the MBH, and glucose appetition.