Functional Integration of Adult-Generated Neurons in Diabetic Goto-Kakizaki Rats

Adult-born neurons in the dentate gyrus (DG) make important contributions to learning as they integrate into neuronal networks. Neurogenesis is dramatically reduced by a number of conditions associated with cognitive impairment, including type 2 diabetes mellitus (T2DM). Increasing neurogenesis may thus provide a therapeutic target for ameliorating diabetes-associated cognitive impairments, but only if new neurons remain capable of normal function. To address the capacity for adult-generated neurons to incorporate into functional circuits in the hyperglycemic DG, we measured Egr1 expression in granule cells (GCs), BrdU labeled four weeks prior, in Goto-Kakizaki (GK) rats, an established model of T2DM, and age-matched Wistars. The results indicate that while fewer GCs are generated in the DG of GK rats, GCs that survive readily express Egr1 in response to spatial information. These data demonstrate that adult-generated GCs in the hyperglycemic DG remain functionally competent and support neurogenesis as a viable therapeutic target.

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Protein-Tyrosine Phosphatase 1B (PTP1B): A Novel Therapeutic Target for Type 2 Diabetes Mellitus, Obesity and Related States of Insulin Resistance

Current Drug Targets - Immune Endocrine & Metabolic Disorders ◽

10.2174/1568008013341163 ◽

2001 ◽

Vol 1 (3) ◽

pp. 265-275 ◽

Cited By ~ 86

Author(s):

B.J. Goldstein

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Protein Tyrosine Phosphatase ◽

Therapeutic Target ◽

Tyrosine Phosphatase ◽

Protein Tyrosine Phosphatase 1B ◽

Novel Therapeutic

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Type 2 diabetes mellitus in the Goto-Kakizaki rat impairs microvascular function and contributes to premature skeletal muscle fatigue

Journal of Applied Physiology ◽

10.1152/japplphysiol.00751.2018 ◽

2019 ◽

Vol 126 (3) ◽

pp. 626-637 ◽

Cited By ~ 6

Author(s):

Jefferson C. Frisbee ◽

Matthew T. Lewis ◽

Jonathan D. Kasper ◽

Paul D. Chantler ◽

Robert W. Wiseman

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Type 2 Diabetes Mellitus ◽

Structure Function ◽

Vascular Structure ◽

Gk Rats ◽

The Impact

Despite extensive investigation into the impact of metabolic disease on vascular function and, by extension, tissue perfusion and organ function, interpreting results for specific risk factors can be complicated by the additional risks present in most models. To specifically determine the impact of type 2 diabetes without obesity on skeletal muscle microvascular structure/function and on active hyperemia with elevated metabolic demand, we used 17-wk-old Goto-Kakizaki (GK) rats to study microvascular function at multiple levels of resolution. Gracilis muscle arterioles demonstrated blunted dilation to acetylcholine (both ex vivo proximal and in situ distal arterioles) and elevated shear (distal arterioles only). All other alterations to reactivity appeared to reflect compromised endothelial function associated with increased thromboxane (Tx)A2 production and oxidant stress/inflammation rather than alterations to vascular smooth muscle function. Structural changes to the microcirculation of GK rats were confined to reduced microvessel density of ~12%, with no evidence for altered vascular wall mechanics. Active hyperemia with either field stimulation of in situ cremaster muscle or electrical stimulation via the sciatic nerve for in situ gastrocnemius muscle was blunted in GK rats, primarily because of blunted functional dilation of skeletal muscle arterioles. The blunted active hyperemia was associated with impaired oxygen uptake (V̇o2) across the muscle and accelerated muscle fatigue. Acute interventions to reduce oxidant stress (TEMPOL) and TxA2 action (SQ-29548) or production (dazmegrel) improved muscle perfusion, V̇o2, and muscle performance. These results suggest that type 2 diabetes mellitus in GK rats impairs skeletal muscle arteriolar function apparently early in the progression of the disease and potentially via an increased reactive oxygen species/inflammation-induced TxA2 production/action on network function as a major contributing mechanism. NEW & NOTEWORTHY The impact of type 2 diabetes mellitus on vascular structure/function remains an area lacking clarity. Using diabetic Goto-Kakizaki rats before the development of other risk factors, we determined alterations to vascular structure/function and skeletal muscle active hyperemia. Type 2 diabetes mellitus reduced arteriolar endothelium-dependent dilation associated with increased thromboxane A2 generation. Although modest microvascular rarefaction was evident, there were no other alterations to vascular structure/function. Skeletal muscle active hyperemia was blunted, although it improved after antioxidant or anti-thromboxane A2 treatment.

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Plasmolipin and Its Role in Cell Processes

Molecular Biology ◽

10.1134/s0026893321050113 ◽

2021 ◽

Vol 55 (6) ◽

pp. 773-785

Author(s):

A. A. Shulgin ◽

T. D. Lebedev ◽

V. S. Prassolov ◽

P. V. Spirin

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Intracellular Signaling ◽

Intracellular Transport ◽

Virus Entry ◽

Normal Function ◽

Normal Functions ◽

Cell Processes ◽

Main Component

Abstract The mechanisms involved in the origin and development of malignant and neurodegenerative diseases are an important area of modern biomedicine. A crucial task is to identify new molecular markers that are associated with rearrangements of intracellular signaling and can be used for prognosis and the development of effective treatment approaches. The proteolipid plasmolipin (PLLP) is a possible marker. PLLP is a main component of the myelin sheath and plays an important role in the development and normal function of the nervous system. PLLP is involved in intracellular transport, lipid raft formation, and Notch signaling. PLLP is presumably involved in various disorders, such as cancer, schizophrenia, Alzheimer’s disease, and type 2 diabetes mellitus. PLLP and its homologs were identified as possible virus entry receptors. The review summarizes the data on the PLLP structure, normal functions, and role in diseases.

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Impact of Bariatric Surgery on Ghrelin and Obestatin Levels in Obesity or Type 2 Diabetes Mellitus Rat Model

Journal of Diabetes Research ◽

10.1155/2014/569435 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Donglei Zhou ◽

Xun Jiang ◽

Weixing Ding ◽

Dingyu Zhang ◽

Lei Yang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Bariatric Surgery ◽

Type 2 Diabetes Mellitus ◽

Weight Control ◽

Sham Operation ◽

Gk Rats ◽

Obese Rats ◽

To Receive

We aimed to evaluate the therapeutic efficacy on weight control by different bariatric surgeries and investigate the ghrelin and obestatin changes after these surgeries in obesity and nonobese type 2 diabetes mellitus (T2DM) rats. Obese rats were randomly assigned to receive sleeve gastrectomy (SG,n=8), minigastric bypass (MGBP,n=8), roux-en-Y gastric bypass (RYGBP,n=8), and sham operation (SO,n=4). Another 4 rats served as control. Besides, Goto-Kakisaki (GK) rats were also randomly divided into similar groups except for total gastrectomy (TG,n=8) group. The results showed that in obese rats, weigh loss in RYGBP group was similar to that in MGBP group but larger than that in SG group. Ghrelin significantly increased in RYGB group, but obestatin increased in MGBP group. Ghrelin/obestatin ratio significantly decreased in SG group. In GK rats, weight loss was most obvious in TG group. Postoperatively, ghrelin was significantly increased in MGBP and RYGB groups but decreased in TG group. Obestatin also showed an increase in MGBP and RYGB groups. Ghrelin/obestatin in TG group decreased significantly. In conclusion, RYGB and MGBP may be more suitable for obese rats, but TG may be the best strategy for T2DM rats to control weight with different mechanisms.

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