Inhibition of progressive reduction of islet β-cell mass in spontaneously diabetic Goto-Kakizaki rats by α-glucosidase inhibitor

Koyama, Motomichi; Wada, Ryuichi; Mizukami, Hiroki; Sakuraba, Hiroyasu; Odaka, Hiroyuki; Ikeda, Hitoshi; Yagihashi, Soroku

doi:10.1016/s0026-0495(00)90242-7

Cited by 49 publications

(25 citation statements)

References 24 publications

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“…␣-Glucosidase inhibitors reduce glucose absorption by inhibiting disaccharide digestion, and thus delay the subsequent monosaccharide absorption. Several reports demonstrated that oral administration of specific ␣-glucosidase inhibitors could effectively improve hyperglycemia as well as diabetic complications (33,34). The present results support the role of oligomers as ␣-glucosidase inhibitors, suggesting their promising potential against diabetes-related pathological conditions.…”

Section: Discussionsupporting

confidence: 84%

Inhibitory Activities of Proanthocyanidins from Persimmon against Oxidative Stress and Digestive Enzymes Related to Diabetes

Lee

Cho

Tanaka

et al. 2007

J Nutr Sci Vitaminol

159

105

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SummaryThe present study was carried out to evaluate the promising potential of polymers and oligomers from proanthocyanidins of persimmon peel as antioxidants and therapeutic agents for diabetes. Both polymers and oligomers showed the scavenging effect of 2,2-diphenyl-1-picrylhydrazyl, with IC 50 values of 4.35 and 2.41 g/mL, respectively, and they also showed a protective activity against protein oxidation induced by 2,2 ′ -azobis (2-amidinopropane) dihydrochloride. In particular, oligomers exerted a stronger activity against free radicals than polymers. In addition, to investigate their protective potential against diabetesrelated pathological conditions, their inhibitory activities on digestive enzymes and advanced glycation endproduct (AGE) formation were evaluated. Polymers showed a strong inhibitory activity against ␣ -amylase, while oligomers had a relatively weak effect. This suggests that the inhibition of ␣ -amylase activity would probably depend on the degree of polymerization. On the other hand, against ␣ -glucosidase activity and AGE formation, oligomers exerted a stronger protective effect than polymers. The present study suggests that polymers and oligomers from proanthocyanidins of persimmon peel could play a role as antidiabetic agents with antioxidative effects. Moreover, oligomers rather than polymers from proanthocyanidins of persimmon peel may be expected to be a more promising antioxidative and antidiabetic agent in relation to utilization in biological systems.

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Section: Discussionsupporting

confidence: 84%

Inhibitory Activities of Proanthocyanidins from Persimmon against Oxidative Stress and Digestive Enzymes Related to Diabetes

Lee

Cho

Tanaka

et al. 2007

J Nutr Sci Vitaminol

159

105

View full text Add to dashboard Cite

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“…Tissue samples from representative non-diabetic subject (NDM-12) show strong positive expression of transcripts in the central area of the islet (A, 240), whereas in the sections from a representative from the diabetic subject (B, DM-13, 120) positive area of (pro)insulin-mRNA positive cells appears to be slightly reduced even though the intensity of the reaction was well preserved. In an islet with severe amyloid deposition, (pro)insulin-mRNA appeared to be well preserved in areas near the amyloid deposition (C, DM-14, 120) vival [44,45]. Although we were not able to demonstrate the presence of apoptotic beta cells in our diabetic subjects, reduced beta-cell mass is probably due to the premature death of beta cells.…”

Section: Discussionmentioning

confidence: 66%

“…Although we were not able to demonstrate the presence of apoptotic beta cells in our diabetic subjects, reduced beta-cell mass is probably due to the premature death of beta cells. Because depletion of beta-cell mass is prevented in geneticallydetermined Type II diabetic rats by metabolic control [45], or aggravated by sucrose feeding [14,18], exaggerated glucotoxicity or lipotoxicity is believed to initiate accelerated beta-cell loss in the advanced stage of Type II diabetes [1, 2, 46±48]. Recent studies of animal models have shown that accelerated beta-cell loss is associated with excessive oxidative stress [14,18], identified by increased expression of HNE and 8-OHdG in the islets of sucrose-fed diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients

et al. 2002

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Impaired insulin secretion and insulin resistance are a characteristic feature of Type II (non-insulin-dependent) diabetes mellitus [1,2]. In spite of extensive studies on the pathophysiology of diabetes, islet pathology and its pathogenesis remain controversial.Classical studies using histochemical methods to identify endocrine cells have reported varying results, including the severe loss of beta cells [3], modest changes with amyloid deposition [4,5] and even no change of islet beta-cell population [6]. Immunohistochemical techniques for the identification of specific populations of islet endocrine cells, showed a nearly 50 % reduction in beta-cell volume density in European Type II non-obese diabetic patients compared with non-diabetic control subjects [7]. Other studies have reported a 24 % reduction of islet beta-cell area density, a 58 % increase in A cell area density and a deposition of amyloid that correlated with the severity of islet pathology [8]. In another study of European Type II diabetic patients, a separate research group has reported Diabetologia (2002) Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients Abstract Aims/hypothesis. We examined the pancreatic islet lesions in Japanese patients with Type II diabetes mellitus to determine if the damage was related to oxidative stress. Methods. Morphometric analyses were performed on immunostained sections of the tail portion of the pancreas from 14 diabetic and 15 non-diabetic patients. Amyloid deposition and oxidative stress-induced tissue damage were evaluated by Congo-red staining and immunostaining. Resistance to oxidative stress was assessed from immunostaining results for Cu, Zn-superoxide dismutase (SOD). Expression of (pro)insulin mRNA was assessed by in situ hybridisation. Results. The pancreas from diabetic patients had amyloid deposition in about 15 % of the islets, intensified reactions of 8-OHdG and HNE, as well as reduced expression of SOD. Islet volume density of beta cells and total beta-cell mass in the pancreas from diabetic patients were reduced by 22 % (p < 0.001) and 30 % (p < 0.05). Islet volume density and total mass of (pro)insulin mRNA-positive cells were similarly reduced in diabetic patients by 22 % (p < 0.001) and 39 % (p < 0.05), respectively. Islet volume density of A cells was increased by 20 % (p < 0.001) but total mass did not change. There were no changes in volume densities of islet, D and PP cells. Reduced beta-cell volume density correlated with increased positive staining of 8-OHdG. Conclusion/interpretation. Japanese Type II diabetic patients show a reduction of beta-cell mass and evidence of increased oxidative stress-related tissue damage that is correlated with the extent of the beta-cell lesions. [Diabetologia (2002) 45: 85±96]

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“…The delay of hyperglycemia appearance in the GLP-1Ϫ or Ex-4Ϫtreated GK rats may be viewed as instrumental in maintaining enhanced ␤-cell mass, resulting in an increased ␤-cell mass 7 weeks after the end of GLP-1 or Ex-4 treatment, in accordance with the concept of glucose toxicity targeted to the ␤-cell mass (22). Such a concept is especially relevant to the situation in the GK model for two reasons: first, when adult GK rats are fed with a carbohydrate-rich diet for 6 weeks, hyperglycemia worsens and is accompanied by a further 50% reduction of ␤-cell mass compared with GK rats fed a normal diet (23), and second, treatment with an ␣-glucosidase inhibitor (voglibose) limits the reduction of ␤-cell mass in GK rats via a reduction of their basal hyperglycemia (24).…”

Section: Glp-1 Promotes ␤-Cell Developmentmentioning

confidence: 99%

Persistent Improvement of Type 2 Diabetes in the Goto-Kakizaki Rat Model by Expansion of the β-Cell Mass During the Prediabetic Period With Glucagon-Like Peptide-1 or Exendin-4

et al. 2002

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In the Goto-Kakizaki (GK) rat, a genetic model of type 2 diabetes, the neonatal ␤-cell mass deficit is considered to be the primary defect leading to basal hyperglycemia, which is detectable for the first time 3 weeks after birth. We investigated in GK females the short-and the longterm effects of a treatment with glucagon-like peptide-1 (GLP-1) or its long-acting analog exendin-4 (Ex-4) during the first postnatal week (during the prediabetic period). GK rats were treated with daily injections of glucagon-like peptide-1 (400 g ⅐ kg ؊1 ⅐ day ؊1 ) or Ex-4 (3 g ⅐ kg ؊1 ⅐ day ؊1 ) from day 2 to day 6 after birth and were evaluated against Wistar and untreated GK rats. Under these conditions, on day 7 both treatments enhanced pancreatic insulin content and total ␤-cell mass by stimulating ␤-cell neogenesis and regeneration. Follow-up of biological characteristics from day 7 to adult age (2 months) showed that such a GLP-1 or Ex-4 treatment exerted long-term favorable influences on ␤-cell mass and glycemic control at adult age. As compared to untreated GK rats, 2-month-old treated rats exhibited significantly decreased basal plasma glucose. Their glucose-stimulated insulin secretion, in vivo after intravenous glucose load or in vitro using isolated perfused pancreas, was slightly improved. This contributed at least partly to improve the in vivo plasma glucose disappearance rate, which was found to be increased in both treated GK groups compared to the untreated GK group. These findings in the GK model indicated, for the first time, that GLP-1 or Ex-4 treatment limited to the prediabetic period delays the installation and limits the severity of type 2 diabetes. Under these conditions, GLP-1 represents a unique tool because of its ␤-cell replenishing effect in spontaneously diabetic rodents. It may prove to be an invaluable agent for the prevention of human type 2 diabetes. Diabetes

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Inhibition of progressive reduction of islet β-cell mass in spontaneously diabetic Goto-Kakizaki rats by α-glucosidase inhibitor

Cited by 49 publications

References 24 publications

Inhibitory Activities of Proanthocyanidins from Persimmon against Oxidative Stress and Digestive Enzymes Related to Diabetes

Inhibitory Activities of Proanthocyanidins from Persimmon against Oxidative Stress and Digestive Enzymes Related to Diabetes

Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese Type II diabetic patients

Persistent Improvement of Type 2 Diabetes in the Goto-Kakizaki Rat Model by Expansion of the β-Cell Mass During the Prediabetic Period With Glucagon-Like Peptide-1 or Exendin-4

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