Streptozotocin induced diabetes as a model of phrenic nerve neuropathy in rats

Department of Biological Sciences, School of Medicine of Triângulo Mineiro, Uberaba, MG, Brazil.
Journal of Neuroscience Methods (Impact Factor: 2.05). 04/2006; 151(2):131-8. DOI: 10.1016/j.jneumeth.2005.06.024
Source: PubMed


Phrenic neuropathies are increasingly recognized in peripheral neuropathies but reports on experimental models of the phrenic nerves diabetic neuropathy are scanty. In the present study, we investigated the phrenic nerve neuropathy, due to experimental diabetes induced by streptozotocin (STZ) and the evolution of this neuropathy in diabetic rats treated with insulin. Proximal and distal segments of the left and right phrenic nerves were morphologically and morphometrically evaluated, from rats rendered diabetic for 12 weeks, by injection of STZ. Control rats received vehicle. Treated rats received a single subcutaneous injection of insulin on a daily basis. The nerves were prepared for light microcopy study by means of conventional techniques. Morphometry was carried out with the aid of computer software. The phrenic nerves of diabetic rats showed smaller myelinated axon diameters compared to controls. The g ratio was significantly smaller for myelinated fibers from diabetic rats compared to controls. Insulin treatment prevented these alterations. Histograms of size distribution for myelinated fibers and axons from control rats were bimodal. For diabetic animals, the myelinated fiber histogram was bimodal while the axon distribution turned to be unimodal. Insulin treatment also prevented these alterations. Our results confirm the phrenic nerve neuropathy in this experimental model of diabetes and suggest that conventional insulin treatment was able to prevent and/or correct the myelinated axon commitment by diabetes.

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    • "Despite the fact that the literature describes preferably a reduction of the myelinated fiber and axon sizes in somatic nerves of STZ-induced diabetic rats [31-33] our results show, in an essentially autonomic nerve, a small myelinated fibers loss, accompanied by degeneration and atrophy of the unmyelinated fibers, in this model of diabetes. This is suggestive that somatic and autonomic nerves react in distinct ways to diabetes. "
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    ABSTRACT: Despite the evidence that renal hemodynamics is impaired in experimental diabetes, associated with glomeruli structural alterations, renal nerves were not yet investigated in experimental models of diabetes and the contribution of nerve alterations to the diabetic nephropathy remains to be investigated. We aimed to determine if ultrastructural morphometric parameters of the renal nerves are affected by short term and/or long term experimental diabetes and if insulin treatment reverses these alterations. Left renal nerves were evaluated 15 days or 12 weeks (N = 10 in each group) after induction of diabetes, with a single injection of streptozotocin (STZ). Control rats (N = 10 in each group) were injected with vehicle (citrate buffer). Treated animals (N = 10 in each group) received a single subcutaneous injection of insulin on a daily basis. Arterial pressure, together with the renal nerves activity, was recorded 15 days (short-term) or 12 weeks (long-term) after STZ injection. After the recordings, the renal nerves were dissected, prepared for light and transmission electron microscopy, and fascicle and fibers morphometry were carried out with computer software. The major diabetic alteration on the renal nerves was a small myelinated fibers loss since their number was smaller on chronic diabetic animals, the average morphometric parameters of the myelinated fibers were larger on chronic diabetic animals and distribution histograms of fiber diameter was significantly shifted to the right on chronic diabetic animals. These alterations began early, after 15 days of diabetes induction, associated with a severe mitochondrial damage, and were not prevented by conventional insulin treatment. The experimental diabetes, induced by a single intravenous injection of STZ, in adult male Wistar rats, caused small fiber loss in the renal nerves, probably due to the early mitochondrial damage. Conventional treatment with insulin was able to correct the weight gain and metabolic changes in diabetic animals, without, however, correcting and / or preventing damage to the thin fibers caused by STZ-induced diabetes. The kidney innervation is impaired in this diabetic model suggesting that alterations of the renal nerves may play a role in the development of the diabetic nephropathy.
    BMC Neuroscience 01/2014; 15(1):5. DOI:10.1186/1471-2202-15-5 · 2.67 Impact Factor
    • "Recent studies have shown that distal and smaller nerve fibers are more sensitive to hyperglycemia, but methods used to detect small fiber neuropathies are difficult and expensive for the routine examination.[3] The electrophysiological methods that investigate the patterns of nerve involvement in DM have been performed by testing different peripheral nerves; however involvement in the same peripheric nerve segment is not clear.[4] "
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    ABSTRACT: Routine conduction studies reflect the summation of all nerve fibers in a peripheral nerve. Nerve fiber groups to distal, small muscles have smaller diameters than the ones to large proximal muscles. There may be minimal differences between the diameters of nerve fiber groups innervating different muscles; even they are all same type of fibers. So, in neuropathic processes some nerve fiber groups may be more seriously affected. 14 rats ( 7 diabetic, 7 control) were studied. Tibial nerve was stimulated from two points and while recorded from a distal (foot intrinsic muscles) and a proximal (gastrocnemius) muscle. There was a significant difference between the proximal and distal recorded conduction velocities. Both proximal and distal recorded conduction velocities decreased during the hyperglycemic process. Our method successfully demonstrated different nerve fiber groups; but, the neuropathic process seemed to be homogeneous in both fiber groups.
    03/2013; 4(1):9-12. DOI:10.4103/0976-3147.105602
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    • "GLP-1 and GIP play an important physiological role in regulation of blood glucose levels[6],[9]. Meal ingestion stimulates the release of incretins, which stimulate insulin synthesis and release (GLP-1 and GIP), suppress glucagon release (GLP-1), delay gastric emptying (GLP-1), and increase satiety (GLP-1)[16]-[18]. "
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    ABSTRACT: Diabetic neuropathies are a family of nerve disorders caused by diabetes. Symptoms of the disease include nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, painful polyneuropathy, autonomic neuropathy, and thoracoabdominal neuropathy. In this study, type 2 diabetes in rats was induced with nicotinamide-streptozotocin. Drug treatment was initiated on the d 15, with the combination regimen of metformin, pioglitazone and glimipiride or metformin and sitagliptin or sitagliptin, amitriptyline and sitagliptin and led to significantly improved glycemic control, increased grip strength and paw jumping response on d 21, 28 and 35 (P < 0.001). Significant increases in blood protein levels and decreases in urinary protein levels were observed in the animals treated with the different regimens on d 21, 28 and 35 (P < 0.001). Combined treatment of streptozotocin and nicotinamide caused marked degeneration of nerve cells, while administration of metformin and sitagliptin showed tissue regeneration and no body weight gain. In conclusion, treatment with sitagliptin and sitagliptin combined with metformin or amitriptyline results in no body weight gain, but causes an increase in grip strength and pain sensitivity, exhibits neural protection, and reverses the alteration of biochemical parameters in rats with streptozotocin-nicotinamide induced type 2 diabetes.
    05/2012; 26(3):200-10. DOI:10.7555/JBR.26.20110054
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