scholarly journals The Effects of Streptozotocin-Induced Diabetes and Insulin Treatment on Carnitine Biosynthesis and Renal Excretion

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6872
Author(s):  
Aman Upadhyay ◽  
Kate E. Boyle ◽  
Tom L. Broderick
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Treatment ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Diabetic Rats ◽  
Free Carnitine ◽  
Organic Cation Transporter 2 ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes

Carnitine insufficiency is reported in type 1 diabetes mellitus. To determine whether this is accompanied by defects in biosynthesis and/or renal uptake, liver and kidney were obtained from male Sprague-Dawley rats with streptozotocin-induced diabetes. Diabetic rats exhibited the metabolic consequences of type 1 diabetes, including hypoinsulinemia, hyperglycemia, and increased urine output. Systemic hypocarnitinemia, expressed as free carnitine levels, was evident in the plasma, liver, and kidney of diabetic rats. Compared to control rats, the low free carnitine in the plasma of diabetic rats was accompanied by decreased expression of γ-butyrobetaine hydroxylase in liver and kidney, suggesting impaired carnitine biosynthesis. Expression of organic cation transporter-2 in kidney was also reduced, indicating impaired renal reabsorption, and confirmed by the presence of elevated levels of free carnitine in the urine of diabetic rats. Insulin treatment of diabetic rats reversed the plasma hypocarnitinemia, increased the free carnitine content in both kidney and liver, and prevented urinary losses of free carnitine. This was associated with increased expression of γ-butyrobetaine hydroxylase and organic cation transporter-2. The results of our study indicate that type 1 diabetes induced with streptozotocin disrupts carnitine biosynthesis and renal uptake mechanisms, leading to carnitine insufficiency. These aberrations in carnitine homeostasis are prevented with daily insulin treatment.

scholarly journals Immediate Insulin Treatment Prevents Diabetes-Induced Gut Region-Specific Increase in the Number of Myenteric Serotonergic Neurons

2021 ◽  
Vol 11 (13) ◽  
pp. 5949
Author(s):  
Diána Mezei ◽  
Nikolett Bódi ◽  
Zita Szalai ◽  
Zsuzsanna Márton ◽  
János Balázs ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Treatment ◽  
Control Level ◽  
Gastrointestinal Symptoms ◽  
Diabetic Rats ◽  
Myenteric Neurons ◽  
Specific Increase ◽  
Neuronal Number ◽  
And Control

To evaluate the effects of hyperglycemia and insulin treatment on the proportion of serotonin-immunoreactive (5-HT-IR) myenteric neurons, samples were taken from the duodenum, ileum, and colon of diabetic, insulin-treated diabetic, and control rats 10 weeks after the onset of streptozotocin-induced hyperglycemia. Myenteric whole-mount preparations were immunostained with anti-5-HT and pan-neuronal anti-HuCD markers. In controls, the 5-HT-IR myenteric neurons represent a small proportion (~2.5%) of the total neuronal number in the investigated gut segments. The proportion of 5-HT-IR myenteric neurons was significantly higher in the duodenum (p < 0.01) and colon (p < 0.0001) of diabetic rats compared to the controls but exhibited a slight increase in the ileum. Immediate insulin treatment resulted in a significantly lower proportion of myenteric 5-HT-IR neurons in each segment (duodenum p < 0.0001; ileum p < 0.01; and colon p < 0.0001) compared to the untreated diabetics. Our study demonstrates that the proportion of 5-HT-IR myenteric neurons was enhanced in type 1 diabetes in a region-specific manner. Immediate insulin treatment prevents a higher hyperglycemia-induced amount of 5-HT-IR neurons and restores it to the control level in each investigated gut segment. Despite the low proportion of 5-HT-IR myenteric neurons, hyperglycemia-related changes of these neurons may play a crucial role in gastrointestinal symptoms in type 1 diabetes.

scholarly journals Swimming Training Does Not Affect the Recovery of Femoral Midshaft Structural and Mechanical Properties in Growing Diabetic Rats Treated with Insulin

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 786
Author(s):  
Gilton de Jesus Gomes ◽  
Márcia Ferreira da Silva ◽  
Edson da Silva ◽  
Ricardo Junqueira Del Carlo ◽  
Daise Nunes Queiroz da Cunha ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Type 1 Diabetes ◽  
Cortical Thickness ◽  
Insulin Treatment ◽  
Maximum Load ◽  
Diabetic Rats ◽  
Swimming Training ◽  
Growing Rats ◽  
Severe Type

Background: The effects of swimming training associated with insulin treatment on the cortical bone health in young rats with severe type 1 diabetes remain unclear, although there is evidence of such effects on the cancellous bone. This study examined the effects of swimming training combined with insulin therapy on the femoral midshaft structural and mechanical properties in growing rats with type 1 diabetes. Methods: Male Wistar rats were divided into six groups (n = 10): control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary plus insulin and diabetic exercise plus insulin. Diabetic rats received an injection (60 mg/kg body weight) of streptozotocin (STZ). Exercised animals underwent a swimming program for eight weeks. Results: Diabetes induced by STZ decreased the bone mineral content (BMC) and density (BMD), and cortical thickness and maximum load and tenacity in the femoral midshaft. Insulin treatment partially counteracted the damages induced by diabetes on BMC, BMD and cortical thickness and tenacity. Swimming training did not affect the femoral structural and mechanical properties in diabetic rats. The combination of treatments did not potentiate the insulin effects. In conclusion, swimming training does not affect the benefits of insulin treatment on the femoral midshaft structural and mechanical properties in growing rats with severe type 1 diabetes.

Vasopressin V1 and V2 receptors in diabetes mellitus

1994 ◽  
Vol 266 (2) ◽  
pp. E217-E223 ◽  
Author(s):  
D. Trinder ◽  
P. A. Phillips ◽  
J. M. Stephenson ◽  
J. Risvanis ◽  
A. Aminian ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Inositol Phosphate ◽  
Free Water ◽  
Diabetic Rats ◽  
Biological Responses ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes ◽  
V2 Receptor ◽  
Plasma Arginine ◽  
Long Acting

Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.

scholarly journals The effects of exercise training versus intensive insulin treatment on skeletal muscle fibre content in type 1 diabetes mellitus rodents

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
David P. McBey ◽  
Michelle Dotzert ◽  
C. W. J. Melling
Keyword(s):  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Type 1 Diabetes ◽  
Exercise Training ◽  
Muscle Fibre ◽  
Lipid Content ◽  
Fibre Type ◽  
Insulin Treatment ◽  
Type I

Abstract Background Intensive-insulin treatment (IIT) strategy for patients with type 1 diabetes mellitus (T1DM) has been associated with sedentary behaviour and the development of insulin resistance. Exercising patients with T1DM often utilize a conventional insulin treatment (CIT) strategy leading to increased insulin sensitivity through improved intramyocellular lipid (IMCL) content. It is unclear how these exercise-related metabolic adaptations in response to exercise training relate to individual fibre-type transitions, and whether these alterations are evident between different insulin strategies (CIT vs. IIT). Purpose: This study examined glycogen and fat content in skeletal muscle fibres of diabetic rats following exercise-training. Methods Male Sprague-Dawley rats were divided into four groups: Control-Sedentary, CIT- and IIT-treated diabetic sedentary, and CIT-exercised trained (aerobic/resistance; DARE). After 12 weeks, muscle-fibre lipids and glycogen were compared through immunohistochemical analysis. Results The primary findings were that both IIT and DARE led to significant increases in type I fibres when compared to CIT, while DARE led to significantly increased lipid content in type I fibres compared to IIT. Conclusions These findings indicate that alterations in lipid content with insulin treatment and DARE are primarily evident in type I fibres, suggesting that muscle lipotoxicity in type 1 diabetes is muscle fibre-type dependant.

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