Effect of low-dose insulin on spinal N-methyl-D-aspartate receptor levels and the downstream signals in streptozotocin-induced diabetic rats
Jiachao Wang, Jinsong Zhang, Wenjia Sun, Jie Sun, Ruomei Qi, Tao Gong, Yun Jiang
Published 2016-04-14
Cite as Chin J Geriatr, 2016, 35(4): 432-436. DOI: 10.3760/cma.j.issn.0254-9026.2016.04.020
Abstract
ObjectiveTo investigate the effect and its significance of low-dose insulin on N-methyl-D-aspartate receptor (NMDAR) level and its downstream signaling of c-Jun N-terminal kinase(JNK) and the extracellular signal-regulated protein kinase (ERK, p44/42MAPK) in streptozotocin-induced diabetic rats.
MethodsTen-week-old male SD rats were randomly divided into 3 groups: control group, diabetic group and insulin-treated diabetes group.Diabetes was induced by streptozocin (STZ, 60mg/kg) injected intraperitoneally.Two weeks after STZ injection, insulin glargine (92u/day for 8 weeks) was subcutaneously injected in the insulin-treated diabetes group.Then, the rat lumbar spinal cords were collected.The protein levels of phospho-Insulin receptor substrate 1(P-IRS1), phospho-NMDAR NR1 subunit (P-NR1), P-JNK and P-p44/42MAPK were evaluated by Western blotting.One week before the terminal of the study, paw thermal response latency was measured in all groups.
ResultsBlood glucose levels were tremendously high in both the diabetic group and insulin-treated diabetes group.Compared with the control group, paw thermal response latency was markedly shortened in the diabetic group (P<0.001) and the insulin-treated diabetes group (P<0.001), and the alteration was more pronounced in the diabetic group (P<0.05). Compared with the control group, the protein levels of P-IRS1, P-NR1, P-JNK and P-p44/42MAPK were increased by 79.2%, 35.1%, 47.6%, 64.3% and 87.6%, respectively in diabetic group and 49.4%, 19.1%, 16.5%, 31.8% and 39.9%, respectively in insulin-treated diabetes group (all P<0.001 or 0.05). In comparison with diabetic group, the increased amplitudes of above 4 parameters were decreased by 29.8%, 16.0%, 31.2%, 32.5% and 47.7% respectively in the insulin-treated diabetes group (all P<0.05).
ConclusionsNMDAR and its downstream signals, such as JNK and p42/44MARK, are involved in the pathogenesis of painful diabetic neuropathy.Although it could not efficiently control the blood glucose level, low-dose insulin treatment may partly inhibit the occurrence of thermal hyperalgesia through inhibiting NMDAR signal pathway.
Key words:
Diabetes mellitus; Neuralgia; Spinal cord; Receptors, N-Methyl-D-Aspartate
Contributor Information
Jiachao Wang
Beijing Insititute of Geriatrics, Beijing 100730, China
Jinsong Zhang
Deparment of Pathology, Beijing Hospital 100730, China
Wenjia Sun
Beijing Insititute of Geriatrics, Beijing 100730, China
Jie Sun
Beijing Insititute of Geriatrics, Beijing 100730, China
Ruomei Qi
Beijing Insititute of Geriatrics, Beijing 100730, China
Tao Gong
Department of Neurology, Beijing Hospital, Beijing 100730, China
Yun Jiang
Department of Neurology, Beijing Hospital, Beijing 100730, China
