Anti-Hyperglycemic Activity of Zinc Plus Cyclo (His-Pro) in Genetically Diabetic Goto-Kakizaki and Aged Rats

Song, Min-Ae; Hwang, Inhwa; Rosenthal, Mark J.; Harris, Diane M.; Yamaguchi, Dean T.; Yip, Ian; Go, Vay Liang W.

doi:10.1177/153537020322801112

Cited by 78 publications

(59 citation statements)

References 40 publications

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“…Cyclo-Z is the only agent able to increase intracellular IDE. In our studies [77], [78] of Cyclo-Z treatment of genetically T2D G-K rats and obese ob/ob mice, plasma insulin levels decreased, while blood glucose decreased and insulin sensitivity increased. Therefore, we conclude that Cyclo-Z treatment increases cellular IDE and improves insulin sensitivity of diabetic rodents.…”

Section: Discussionsupporting

confidence: 47%

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

et al. 2017

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BackgroundAssociation of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice.Scope of reviewMetabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues. Mechanistic effect of insulin degrading enzyme (IDE) in decreasing blood glucose and brain Aβ levels will be elucidated. Cyclo-Z effects on these biochemical parameters will be discussed.Major conclusionStimulation of IDE synthesis is effective for the clinical treatment of metabolic diseases including AD and T2D.General significanceCyclo-Z might be the effective treatment of AD and T2D by stimulating IDE synthesis.

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Section: Discussionsupporting

confidence: 47%

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

et al. 2017

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“…The GK rat is a model of nonobese insulin-resistant T2D (45). Although the GK rat is a derived from a nondiabetic Wistar colony, many studies (52,56) have used euglycemic SD as control for GK rats. The animals were housed at 21°C with 12-h light-dark cycles, fed with standard laboratory chow, and had access to drinking water ad libitum.…”

Section: Methodsmentioning

confidence: 99%

Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes

Ndisang

Lane²,

Jadhav³

2009

American Journal of Physiology-Endocrinology and Metabolism

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Ndisang JF, Lane N, Jadhav A. Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes. Am J Physiol Endocrinol Metab 296: E1029-E1041, 2009. First published February 10, 2008 doi:10.1152/ajpendo.90241.2008.-In type 2 diabetes (T2D), postprandial and fasting hyperglycemia are important predictors of cardiovascular diseases; however, few drugs are currently available to simultaneously suppress these conditions. Here, we report an enduring antidiabetic effect of the heme oxygenase (HO) inducer hemin on Goto-Kakizaki rats (GK), a nonobese insulinresistant T2D model. HO breaks down the heme-moiety-generating antioxidants (biliverdin/bilirubin and ferritin) and carbon monoxide, which stimulate insulin secretion. Hemin induces HO-1 to potentiate HO activity and the HO-derived products. Chronically applied hemin (30 mg/kg ip) for a month reduced and maintained fasting glucose at physiological levels for 3 mo. Before therapy, glucose levels were 9.3 Ϯ 0.3 mmol/l (n ϭ 14). At 1, 2, and 3 mo posttherapy, we recorded 6.7 Ϯ 0.13, 5.9 Ϯ 0.2, and 7.2 Ϯ 0.2 mmol/l, respectively. Hemin was also effective against postprandial hyperglycemia (14.6 Ϯ 1.1 vs. 7.5 Ϯ 0.4 mmol/l; n ϭ 14; P Ͻ 0.01), and the effect remained sustained for 3 mo after therapy. The reduction of hyperglycemia was accompanied by enhanced HO-1, HO activity, and cGMP of the soleus muscle, alongside increased plasma bilirubin, ferritin, SOD, total antioxidant capacity, and insulin levels, whereas markers/mediators of oxidative stress like urinary-8-isoprostane and soleus muscle nitrotyrosine, NF-B, and activator protein-1 and -2 were abated. Furthermore, inhibitors of insulin signaling including soleus muscle glycogen synthase kinase-3 and JNK were reduced, while the insulinsensitizing adipokine, adiponectin, alongside AMPK were increased. Correspondingly, hemin improved glucose tolerance, suppressed insulin intolerance, reduced insulin resistance, and overturned the inability of insulin to enhance glucose transporter 4, a protein required for glucose uptake. Hemin also upregulated HO-1/HO activity and cGMP and lowered glucose in euglycemic Sprague-Dawley control rats albeit less intensely, suggesting greater selectivity of the HO system in diabetic conditions. In conclusion, reduced oxidative stress alongside the concomitant and paradoxical enhancement of insulin secretion and insulin-sensitizing pathways may account for the 3-moenduring antidiabetic effect. The synergistic interaction among HO, adiponectin, and GLUT4 may be explored against insulin-resistant diabetes.adiponectin; insulin resistance; oxidative stress; glucose transporter 4; glycogen synthase kinase-3; nuclear factor-B; activating protein-

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“…shown to improve short term and long term oral glucose tolerance, as weIl as decreased insulin resistance, in aged GK rats (110). This decreased insulin resistance is thought to be due to the supply of new Zn brought into the system through the Zn-CHP complex.…”

Section: -Zinc and Animal Models Of Type 2 Diabetesmentioning

confidence: 99%

“…In yet another recent study, a complex formed between Zn and Cyclo (His-Pro) (CHP), a metabolite of thyrotrophin-releasing hormone or product of peptide or amino acid sources, was studied in the Goto-Kakizaki (GK) rat, a non-obese type 2 diabetes animal model, exhibiting a mild fasting hyperglycaemia (110). CHP metabolism is thought to be directly related to glucose metabolism (110), since STZ-diabetic rats exhibited an increase of CHP levels which decreased after insulin treatment (111), suggesting that blood glucose metabolism is related to gut CHP concentrations (I12).…”

Section: -Zinc and Animal Models Of Type 2 Diabetesmentioning

confidence: 99%

Insulino-mimetic and anti-diabetic effects of zinc

Vardatsikos

Pandey

Srivastava

2013

Journal of Inorganic Biochemistry

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blocked Zn-induced ERKl/2 and PKB phosphorylation, but AG1478, an inhibitor for EGFR was without effect. In CHO cells overexpressing tyrosine kinase deficient IR (CHO-1018), Zn was still able to induce the phosphorylation ERK1/2 and PKB/Akt, whereas insulin-induced ERK1/2 and PKB/Akt phosphorylation was abolished in these cells.Moreover, Zn had no effect on the tyrosine phosphorylation of IR-p-subunit and IRS-l in CHO-IR cells. Furthermore, in IGF-IR knockout cells, both IGF-l and Zn were unable to stimulate the phosphorylation ofERK1/2 and PKB. Taken together, these data suggest that Zn-induced ERK1/2 and PKB/Akt phosphorylation is independent of IR-or EGFR-PTK, but requires IGF-IR-PTK.

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Anti-Hyperglycemic Activity of Zinc Plus Cyclo (His-Pro) in Genetically Diabetic Goto-Kakizaki and Aged Rats

Cited by 78 publications

References 40 publications

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes

Insulino-mimetic and anti-diabetic effects of zinc

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