Research On The Relationship Between Short-term Intensive Insulin Treatment And C-jun N-terminal Kinase And Hemeoxygenase-1 Of The Newly-diagnosed Type 2 Diabetes Mellitus

Objective: IT has been recently revealed that type 2 diabetes (T2DM) is an inflammatory reaction mediated by cytokines. Inflammation plays an important role in insulin resistence (IR) and beta Cell of islet. Furthermore,th- ere are multiple correlations between oxidative activation and inflammation, which can disturb the signal transduction of insulin according to varied signal mechanism,thus results in the incidence of diabetes.There are some studies proclaimed that intensive insulin therapy can improve prognosis of severe ill.And a large sample of clinic study indicated that contrast with oral administration,intensive insulin treatment can improve function of beta Cell and control plasma glucose for a long time much better.These revealed that insulin may have the some other effects except aiti-glucose,such as inhibiting inflammation access,alleviating lipotoxicity and lightenning endoplasmic reticulum stress,so as to improve IR. There are few researches internal and abroad engaged in the mechanism of anti-inflammatory effect of insulin and the difference between intensive and conventional insulin injection. This study compared the c-Jun N-terminal kinase (JNK),c-Jun and Heme oxygenase-1 (HO-1)level between newly-diagnosed T2DM and healthy crowd,further investigated the mechanism of insulin therapy to alleviate inflammation effect and the effect on IR and oxidative stress.Meanwhile,for the treatment of diabetes,more basis will be provided.Methods: There are eighty newly-diagnosed diabetes.According to the random principle,forty one six of them accepted multiple-daily injection of insulin(MDII),the other thirty nine patients accepted twice-daily injections of insulin(TDII).All subjects were treated for two weeks. Additional forty healthy people with the similar BMI to the treatment group were concluded in the control group(NC).Fasting plasm glucose and fasting insulin levels were measured prior and posterior to hospitalization and the healthy ones.Homa-IR and Homa-βwere calculated respectively to evaluate the insulin resistance (IR) status andβ-cell function.Two milliliters anticoagulation blood were extracted to separate mononuclear cells,from which the total mRNA was abstracted.Usi- ng RT-PCR analysis the expression level of c-Jun and HO-1 in peripheral blood cells;using immunocell chemistry analysis the expression level of JNK,c-Jun,HO-1.Results:(1)Before therapy,the patients in intensive treatment group and conventional treatment group had no statistical differences in FPG,2hPG,HbA1c,HOMA-IR and HOMA-β,and these statistics were significantly different from the health control group .All the groups were same in age,BMI and chalesterol(P > 0.10).(2)After theapy,FPG,2hPG and HOMA-IR of the two groups significantly declined compared to the statistics before the treatment.While HOMA-βincreased(P<0.05).MDII group 2hPG declined more significangtly. (P<0.05)(3)Compared to healthy control group,the gene expression levels of c-jun and HO-1 in the two treatment groups both increased (P<0.05).And the levels decreased after therapy than before(P<0.05).The gene expression of c-jun and HO-1 had no statistical differences between MDII and TDII before therapy.But after therapy,the expression significantly decreased in MDII than in the TDII(P<0.05).(4)The protein expression of JNK,c-Jun and HO-1 increased in two therapy groups than in control group(P<0.05). There were no differences between MDII and TDII before the treatment.And the expression of all the factors decreased much more in MDII than in TDII after the treatment.(P<0.05).Conclusions:(1)The expression of JNK,c-Jun and HO-1 significantly increased in T2DM compared to the health control group.It indicated that high plasm glucose induced the oxidative activation,and further stimulaed related inflammation signal passageway.(2)After the therapy,HOMA-IR decreased and HOMA-βincreased obviously,this indicated that both of intensive treatment and conventional treatment can alleviate insulin resistent and improve beta cell of islet function.(3)After the insulin therapy, JNK signal pathway was inhibited, and the expression of JNK,c-Jun and HO-1 declined, which signed that insulin may lighten oxidative and inflammatory reaction by inhibiting JNK signal transduction pathway, thus improve IR.(4)The expression of JNK,c-Jun and HO-1 and 2hPG were significantly different between the two therapy groups after the therapy,which indicated that intensive treatment was better than normal treatment.