This response to amino acids was decreased by 60% when glutamine was omitted. Insulin release by SUR1–/– islets was also stimulated by a ramp of glutamine alone.
In normal islets, methionine sulfoximine, a glutamine synthetase inhibitor,
suppressed insulin release in response to a glucose ramp.
High glucose doubled glutamine levels of islets.
Glutamine has been found to induce "insulin resistance" in fat cells.
Muscle cell glutamine production is increased by insulin.
Suppressing glutamine synthesis suppresses insulin release in response to glucose.
Insulin regulates glucose indirectly. Glutamine production decreases availability of glutamate, which reduces availability of glutamate-derived metabolites necessary to mitochondrial respiration. Less fat is fed into the kreb's cycle, increasing the cell's dependence on fermentation of glucose for energy, which increases the demand for glucose. Remember how exercise can increase glucose uptake without increased insulin? This is apparently why. And they did the study in 2004.
For proper symmetry, I guess it will be necessary that leptin increases the production of glutamate.
No wonder insulin is anabolic. It spares proteins from mitochondrial respiration (krebs cycle)
Methionine sulfoximine inhibition of glucose stimulated insulin secretion was
associated with accumulation of glutamate and aspartate.
I should say that insulin is expressed by the beta cells in reaction to glutamine to facilitate its uptake. Insulin will increase the demand for glutamine in any cell. If pre-made glutamine is not present, the demand for glutamine will be served by the synthesis of glutamine from glutamate. Sometimes I talk right around my main point.
I went back and reread that glutamine inducing insulin secretion study, and they mentioned this;
"Hyperinsulinism and Hyperammonemia in Infants with Regulatory Mutations of the Glutamate Dehydrogenase Gene"
Glutamate dehydrogenase is an enzyme needed to convert glutamate to alpha-keto glutarate, which feeds into the kreb's cycle, and is thus needed to burn fat.
Lets see. Glutamine induces insulin secretion (And insulin induces glutamine production). Excess of an enzyme that breaks glutamate down into alpha keto-glutaric acid induces insulin secretion.
It almost looks like the lack of glutamate induces insulin secretion.
The control of GDH through ADP-ribosylation is particularly important in insulin-producing β cells. Beta cells secrete insulin in response to an increase in the ATP:ADP ratio, and, as amino acids are broken down by GDH into α-ketoglutarate, this ratio rises and more insulin is secreted. SIRT4 is necessary to regulate the metabolism of amino acids as a method of controlling insulin secretion and regulating blood glucose
So what would glutamine do? Spare glutamate, so that it can be made into alpha-keto glutarate?
More alpha keto glutarate. Does the Kreb's cycle use more alpha keto glutarate when glucose is providing acetyl coa? Like, the clock runs faster?
'Tis a slippery beast. Insulin appears to regulate glucose. But not really. Appears to regulate glutamine. But that might just be because glutamine spares glutamate so it can be broken down to alpha keto glutarate.
So it actually appears to create a demand for alpha keto glutarate, and glucose and glutamine merely facilitate this; except that muscle cells produce glutamine in reaction to insulin....
Okay. Muscle cells are pretty heavy on protein. Insulin might stimulate glutamate production from glutamic acid, at the same time providing substrate for both alpha keto glutaric acid and glutamine.
I'm sort of tied in knots.
But I think the proper way of looking at this is probably that insulin doesn't actually try to "regulate" anything. It's probably all about equilibrium, anyways.