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4-Hydroxyisoleucine is an amino acid that has been found in fenugreek (T. foenum graecum) seeds and has antidiabetic activity. It increases glucose-stimulated insulin release from isolated rat islets and isolated perfused rat pancreas when used at a concentration of 200 μM. In vivo, 4-hydroxyisoleucine increases PI3K activity in muscle and liver in rats when administered at a dose of 18 mg/kg and in muscle in a rat model of type 2 diabetes induced by nicotinamide (Item No. 11127) and streptozotocin (STZ; Item No. 13104) when administered at 25 mg/kg. 4-Hydroxyisoleucine (50 mg/kg per day for four weeks) decreases plasma glucose, triglyceride, LDL, HDL, and cholesterol levels in an STZ-induced rat model of type 1 diabetes.

4-hydroxyisoleucine has been extracted and purified from fenugreek seeds, which are known in traditional medicine for their antidiabetic properties. 

(4S)-4-Hydroxy-L-isoleucine is 4S isomer of 4-Hydroxyisoleucine, which is used as a treatment for type II diabetes.

ChEBI: An L-isoleucine derivative that is L-isoleucine bearing a (4S)-hydroxy substituent.

4-Hydroxyisoleucine increases glucose-induced insulin release, in the concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on isolated islets of Langerhans from both rats and humans.