• Preventive Nutrition and Food Science
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• v.22 no.1
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• pp.1-8
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• 2017

About 20 chemical elements are nutritionally essential for humans with defined molecular functions. Several essential and nonessential biometals are either functional nutrients with antidiabetic actions or can be diabetogenic. A key question remains whether changes in the metabolism of biometals and biominerals are a consequence of diabetes or are involved in its etiology. Exploration of the roles of zinc (Zn) in this regard is most revealing because 80 years of scientific discoveries link zinc and diabetes. In pancreatic ${\beta}$- and ${\alpha}$-cells, zinc has specific functions in the biochemistry of insulin and glucagon. When zinc ions are secreted during vesicular exocytosis, they have autocrine, paracrine, and endocrine roles. The membrane protein ZnT8 transports zinc ions into the insulin and glucagon granules. ZnT8 has a risk allele that predisposes the majority of humans to developing diabetes. In target tissues, increased availability of zinc enhances the insulin response by inhibiting protein tyrosine phosphatase 1B, which controls the phosphorylation state of the insulin receptor and hence downstream signalling. Inherited diseases of zinc metabolism, environmental exposures that interfere with the control of cellular zinc homeostasis, and nutritional or conditioned zinc deficiency influence the pathobiochemistry of diabetes. Accepting the view that zinc is one of the many factors in multiple gene-environment interactions that cause the functional demise of ${\beta}$-cells generates an immense potential for treating and perhaps preventing diabetes. Personalized nutrition, bioactive food, and pharmaceuticals targeting the control of cellular zinc in precision medicine are among the possible interventions.

• Journal of Life Science
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• v.22 no.7
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• pp.904-911
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• 2012

Yacon has been used in folk medicines as a medicinal tea for hypoglycemia treatment. In a recent study described herein, antioxidative, antibacterial, antifungal activities, and cell-protective functions of yacon leaves have been reported. To evaluate the effects on fibrosis on pancreatitis, the efficacy of 1% of yacon extract (YE) on dibutyltin dichloride (DBTC) (8 mg/kg)-induced pancreatitis in rats was examined. On the 21st day after the DBTC treatment, a large increase in collagen was observed in the pancreas in the DBTC-treatment group (DT). But this was noticeably decreased with YE. In relation to the expression of COX-2, there was no response or a very weak response in the pancreas of the control group (CON). However, in DT, strong expression of COX-2 was observed in the pancreas on the 14th day, and COX-2 was present in inflammatory cells in the pancreas of the DT, especially on the 21st day. The expression was decreased for YE compared with DT. A remarkable increase in TGF-${\beta}1$ expression was observed in inflammatory cells in the pancreas in DT on the 21st day, whereas the expression was not found in YE after 21 days. However, on the 21th day, TGF-${\beta}1$ expression was increased in acinar cells of YE compared with DT. VEGF expression was very similar to the expression of in the pancreas. These results suggest that YE has an inhibitory effect on DBTC-induced pancreatic fibrosis.

• Journal of Pharmaceutical Investigation
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• v.16 no.3
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• pp.89-100
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• 1986

Although insulin has been available for the treatment of diabetes mellitus for more than half a centry, the deficiency of conventional insulin therapy for diabetic patients have, to this date, not been satisfactorily overcome by any method. The development of potential delivery systems for insulin is highly important to prevent excessive fluctuation of plasma glucose levels, which results in long term complications in the diabetic. There are three major approaches toward development of glucose responding insulin delivery systems: A bioengineering approach is to devise mechanical components capable of releasing insulin in amounts appropriate to varying blood-glucose requirements. A biological approach relies upon cultured, living pancreatic beta cells encapsulated to constitute an insulin delivery unit. A biochemical approach is to synthesize a stable and biologically active glycosylated insulin that is complementary to the binding sites of lectin. This paper will cover several specific areas, including pancreatic transplantation(total or isolated islet cells), artificial pancreases(bioengineering or biological approach), controlled delivery system, glucose sensitive membrane systems, and a self-regulating insulin delivery system.

• Biomedical Science Letters
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• v.20 no.1
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• pp.14-24
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• 2014

Hypoxia is one of the main reasons for islet apoptosis after transplantation as well as during isolation. In this study, we attempted to determine the potential usefulness of NF-${\kappa}B$ inhibitor for suppression of hypoxia-induced ${\beta}$-cell apoptosis as well as the relationship between IP-10 induction and ${\beta}$-cell apoptosis in hypoxia. To accomplish this, we cultured the mouse pancreatic ${\beta}$-cell line MIN6 in hypoxia (1% $O_2$). Among several examined chemokines, only IP-10 mRNA expression was induced under hypoxia, and this induced IP-10 expression was due to NF-${\kappa}B$ activity. Since a previous study suggested that IP-10 mediates ${\beta}$-cell apoptosis, we measured hypoxia-induced IP-10 protein and examined the effect of anti-IP-10 neutralizing Ab on hypoxia-induced ${\beta}$-cell apoptosis. However, IP-10 protein was not detected, and anti-IP-10 neutralizing Ab did not rescue hypoxia-induced MIN6 apoptosis, indicating that there is no relationship between hypoxia-induced IP-10 mRNA expression and hypoxia-induced ${\beta}$-cell apoptosis. Since it was still not clear if NF-${\kappa}B$ functions as an apoptotic or anti-apoptotic mediator in hypoxia-induced ${\beta}$-cell apoptosis, we examined possible involvement of NF-${\kappa}B$ in hypoxia-induced ${\beta}$-cell apoptosis. Treatment with 1 ${\mu}M$ NF-${\kappa}B$ inhibitor suppressed hypoxiainduced apoptosis by more than 50%, while 10 ${\mu}M$ AP-1 or 4 ${\mu}M$ NF-AT inhibitor did not, indicating involvement of NF-${\kappa}B$ in hypoxia-induced ${\beta}$-cell apoptosis. Overall, these results suggest that IP-10 is not involved in hypoxia-induced ${\beta}$-cell apoptosis, and that NF-${\kappa}B$ inhibitor can be useful for ameliorating hypoxia-induced ${\beta}$-cell apoptosis.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.27-31
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• 2002

${\gamma}-Aminobutyric$ Acid (GABA) is contained in pancreatic islet ${\beta}-cells$ although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA $(10,\;30\;and\;100\;{\mu}mol/kg/h),$ given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA $(30\;{\mu}mol/kg/h)$ also further increased the amylase secretion stimulated by CCK (30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA $(10,\;30\;and\;100\;{\mu}mol/kg/h)$ also dose-dependently elevated pancreatic amylase secretion evoked by CCK alone. Bicuculline $(100\;{\mu}mol/kg/h),$ a $GABA_A-receptor$ antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK plus secretin or CCK alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via $GABA_A-receptor$ in anesthetized rats, which may account for elevating the action of CCK released by sodium oleate.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.113-117
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• 2012

FasL, perforin, $TNF{\alpha}$, IL-1 and NO have been considered as effector molecule(s) leading to ${\beta}$-cell death in autoimmune diabetes. However, the real culprit(s) of ${\beta}$-cell destruction have long been elusive despite intense investigation. Previously we have suggested $IFN{\gamma}/TNF{\alpha}$ synergism as the final effector molecules in autoimmune diabetes of NOD mice. A combination of $IFN{\gamma}$ and $TNF{\alpha}$ but neither cytokine alone, induced classical caspase-dependent apoptosis in murine insulinoma and pancreatic islet cells. $IFN{\gamma}$ treatment conferred susceptibility to $TNF{\alpha}$-induced apoptosis on otherwise resistant murine insulinoma cells by STAT1 activation followed by IRF-1 induction. Here we report that $IFN{\gamma}/TNF{\alpha}$ synergism induces apoptosis of human pancreatic islet cells. We also observed STAT1 activation followed by IRF-1 induction by $IFN{\gamma}$ treatment in human islet cells. Taken together, we suggest that $IFN{\gamma}/TNF{\alpha}$ synergism could be involved in human islet cell death in type 1 diabetes, similar to murine type 1 diabetes.

• Journal of Ginseng Research
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• v.34 no.3
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• pp.192-197
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• 2010

Recent studies have indicated that $\beta$-cell dysfunction and insulin resistance are important factors in the development of type 2 diabetes. The present study investigated the effect of extracts from different parts of white, Taegeuk, and red ginseng root on insulin-stimulated glucose uptake in muscle cells and proliferation of $\beta$-cells. Extracts of the fine roots of Taegeuk ginseng significantly enhanced glucose uptake compared with the control. White ginseng lateral root extracts enhanced insulin-induced glucose uptake. Proliferation of $\beta$-cells was significantly increased by Taegeuk ginseng main and lateral root extracts and by red ginseng lateral and fine root extracts. In conclusion, different root parts of white, Taegeuk, and red ginseng differentially affect glucose uptake and pancreatic $\beta$-cell proliferation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.468-473
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• 2007

The antidiabetic effect of Amomum xanthioides(A. xanthioides) extract was investigated. Alloxan caused the hyperglycemia and hypoinsulinemia by a selective destruction of pancreatic ${\beta}$-cell. Pretreatment of mouse with A. xanthiodies extract for 2 days prior to alloxan administration completely protected hyperglycemia induced by alloxan. In addition, administration of A. xanthioides extract to alloxan-induced diabetic mouse significantly abolished hyperglycemia, hypoinsulinemia, and, the reduction of size and number of insulin-secreting cells induced by alloxan. Administration of A. xanthioides extract to alloxan-induced diabetic mouse rapidly increased pancreatic Reg gene expression to 7 days, and then decreased. In alloxan-diabetic mouse. Reg gene expression was increased at 3 days after alloxan injection, and sustained until 24 days. The present results indicate that A. xanthioides extract contains potentially effective components exhibiting both protection and treatment of alloxan-induced diabetes. These results suggested that the antidiabetic effect of A. xanthoides extract may be mediated through the regeneration of pancreatic ${\beta}$-cells.

• Herbal Formula Science
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• v.27 no.3
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• pp.223-236
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• 2019

Dengropanax morfiferus (D), Broussonitia kazinoki (B), and Cudriania tricuspidata (E), a widely cultivated species in South Korea, has been used as traditional medicine to treat numerous diseases. In this study, we evaluated the antidiabetic effects in a various signaling mechanisms using mixed extract and major component contents were analyzed by HPLC in the combined extracts from Dengropanax morfiferus, Broussonitia kazinoki, and Cudriania tricuspidata (DBCE). DBCE inhibited ${\alpha}$-glucosidase and ${\alpha}$-amylase activation and showed potent antioxidant effects, which are evaluated using DPPH, ABTS, and SOD assay. Cytokines, which are released by inflammatory cells in pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. DBCE showed the protective effects in RINm5F cells against cytokines-induced damage by suppressing inducible nitric oxide (NO) synthase and COX-2 expression and NO production. Insulin resistance is the primary characteristic of type 2 diabetes. Therefore, the regulatory effect of DBCE on glucose uptake and production are investigated in insulin-responsive human HepG2 cells. DBCE stimulated glucose uptake, prevented Glut2 and phosphor-IRS1 downregulation induced by high glucose (HG, 30 mM). Moreover, DBCE pretreatment diminished glucose levels, PEPCK and G6Pase overexpression provoked by HG. These findings suggest that DBCE might be used for diabetes treatment through alpha-glucosidase or alpha-amylase activity regulation, pancreatic beta cell protection, hepatic glucose sensitivity improvement. Cytokines, which are released by inflammatory cells' infiltrations around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus.

• Korean Journal of Plant Resources
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• v.25 no.2
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• pp.184-192
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• 2012

The present study was designed to examine the potential antidiabetic and antioxidant effect of ethanol extract from $Prunus$ $mume$ fruit (PME) against alloxan-induced oxidative stress in pancreatic ${\beta}$-cells, HIT-T15. To evaluate the antidiabetic effect of PME, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliu bromide (MTT) cell proliferation assay, lactate dehydrogenase (LDH) release assay, $NAD^+$/NADH ratio and insulin secretion were assessed. We also measured its antioxidant effect against alloxan-induced oxidative stress in the cells by assessing the levels of the antioxidant enzymes including superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx). The results of this analysis showed that alloxan significantly decreased cell viability, increased LDH leakage, and lowered $NAD^+$ /NADH ratio and insulin secretion in HIT-T15 cells. However, PME significantly increased the viability of alloxan-treated cells and lowered LDH leakage. The intracellular $NAD^+$ /NADH ratio and insulin secretion were also increased by 1.5~1.9-fold and 1.4-fold, respectively, after treatment with the PME. The HIT-T15 cells treated with alloxan showed significant decreases in the activities of antioxidant enzymes, while PME significantly elevated the levels of antioxidant enzymes. Based on these results, we suggest that PME could have a protective effect against the cytotoxicity and dysfunction of pancreatic ${\beta}$-cells in the presence of alloxan-induced oxidative stress.