Protective effects of the SGLT2 inhibitor luseogliflozin on pancreatic β‐cells in <i>db/db</i> mice: The earlier and longer, the better

Kimura, Tomohiko; Obata, Atsushi; Shimoda, Masashi; Okauchi, Seizo; Kanda‐Kimura, Yukiko; Nogami, Yuka; Moriuchi, Saeko; Hirukawa, Hidenori; Kohara, Kenji; Nakanishi, Shuhei; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki

doi:10.1111/dom.13400

Cited by 41 publications

(48 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, food intake of group db/db(c+) was greater than that of group db/db(c−), and decreased insulin secretion in group db/db(c−) and preserved insulin secretion in group db/db(c+) were shown by weekly blood collection or OGTT. These results are comparable with previous reports 26,27 .…”

Section: Discussionsupporting

confidence: 93%

Investigation of the preservation effect of canagliflozin on pancreatic beta cell mass using SPECT/CT imaging with 111In-labeled exendin-4

Hamamatsu

Fujimoto

Fujita

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Radiolabeled exendin derivatives are promising for non-invasive quantification of pancreatic beta cell mass (BCM); longitudinal observation of BCM for evaluation of therapeutic effects has not been achieved. The aim of this study is to demonstrate the usefulness of our developing method using [Lys12(111In-BnDTPA-Ahx)]exendin-4 to detect longitudinal changes in BCM. We performed a longitudinal study with obese type 2 diabetes model (db/db) mice administered canagliflozin, which is reported to preserve BCM. Six-week-old mice were assigned to a canagliflozin-administered group or a control group. Blood glucose levels of the canagliflozin group were significantly lower than those of the control group. Plasma insulin levels, insulin secretion during OGTT and insulin content in the pancreas were preserved in the canagliflozin group in comparison with those in the control group. According to SPECT/CT imaging analysis using [Lys12(111In-BnDTPA-Ahx)]exendin-4, pancreatic uptake was significantly decreased in the control group, whereas there was no significant change in the canagliflozin group. After nine weeks, both pancreatic uptake and BCM of the canagliflozin group were significantly higher than those of the control group, and a correlation between them was observed. In conclusion, our imaging method confirmed the BCM-preservation effect of canagliflozin, and demonstrated its potential for longitudinal evaluation of BCM.

show abstract

Section: Discussionsupporting

confidence: 93%

Investigation of the preservation effect of canagliflozin on pancreatic beta cell mass using SPECT/CT imaging with 111In-labeled exendin-4

Hamamatsu

Fujimoto

Fujita

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Owing to increased cell proliferation and decreased β-cell apoptosis, a larger pancreatic β-cell mass was observed in mice treated with luseogliflozin. Additionally, the β-cellrelated factors were significantly increased in the luseogliflozintreated mice, and the insulin gene transcription factors, MafA and PDX1, and insulin levels were increased (62). In empagliflozin-treated mice, the expression levels of βcell-related factors, including insulin, MafA, PDX1, GLP-1 receptor, and glucose transporter Glut2, were increased.…”

Section: Sglt2 Inhibitors Promote the Expression Of Different β-Cell-mentioning

confidence: 95%

Prospect of Sodium–Glucose Co-transporter 2 Inhibitors Combined With Insulin for the Treatment of Type 2 Diabetes

Yang

Zhao

et al. 2020

Front. Endocrinol.

View full text Add to dashboard Cite

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new family of antidiabetic drugs that reduce blood glucose independent of insulin. In this review, we present the advantages and adverse effects of SGLT2 inhibitors plus insulin therapy as a treatment regimen for patients with type 2 diabetes (T2D). Compared with placebo, SGLT2 inhibitors plus insulin therapy could significantly decrease fasting blood glucose and HbA1c, thereby reducing the daily required dose of insulin. A reduction in body weight and improvements in insulin resistance and β-cell function have also been widely reported with this therapy, and other potential advantages, including the reduction in blood pressure, adverse cardiovascular outcomes, and visceral adipose tissue volume, have been revealed. SGLT2 inhibitors cause a greater reduction than dipeptidyl peptidase-4 (DPP-4) inhibitors in body weight and the risk of cardiovascular disease. Furthermore, compared with glucagon-like peptide-1 (GLP-1) agonists, SGLT2 inhibitors reduce blood pressure, and heart failure. As this therapy is an oral preparation, an improvement in patient compliance is also achieved. Despite these advantages, however, combination therapy with SGLT2 inhibitors and insulin has several risks. Although no difference has been found in the incidence of hypoglycemic events and urinary tract infection between the administration of this combination and that of placebo, the risk of genital tract infections was reported to increase with the combination therapy. Additionally, bone adverse effects, euglycemic diabetic ketoacidosis, and volume depletion-and osmotic diuresis-related adverse effects have been observed. Altogether, we could conclude that SGLT2 inhibitors plus insulin therapy is an efficient treatment option for patients with T2D, especially those requiring high daily insulin doses and those with insulin resistance, obesity, and a high risk of cardiovascular events. However, careful monitoring of the adverse effects of this combination is also warranted.

show abstract

“…We speculated that relief from glucotoxicity by LC and SGLT2i could indirectly support to prevent beta-cell death and alpha-cell expansion in part. Some previous reports indicated that beta-cell mass was sustained by treatment with either SGLT2i alone or SGLT2i plus insulin, but not by insulin alone in diabetic rodent models (25)(26)(27). Thus, we speculate that SGLT2i per se might directly protect islet morphology.…”

Section: Discussionmentioning

confidence: 57%

A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor

et al. 2020

View full text Add to dashboard Cite

ObjectiveA low-carbohydrate diet (LC) can be beneficial to obese subjects with type2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 inhibitor (SGLT2i) presents prompt glucose-lowering effects in subjects with T2DM. We investigated how LC and SGLT2i could similarly or differently influence on the metabolic changes, including glucose, lipid, and ketone metabolism in lean insulinopenic Akita mice. We also examined the impacts of the combination.MethodsMale Akita mice were fed ad libitum normal-carbohydrate diet (NC) as a control or low-carbohydrate diet (LC) as an intervention for 8 weeks with or without SGLT2i treatment. Body weight and casual bold glucose levels were monitored during the study, in addition to measuring TG, NEFA, and ketone levels. We quantified gene expressions involved in gluconeogenesis, lipid metabolism and ketogenesis in the liver and the kidney. We also investigated the immunostaining analysis of pancreatic islets to assess the effect of islet protection.ResultsBoth LC and SGLT2i treatment reduced chronic hyperglycemia. Moreover, the combination therapy additionally ameliorated glycemic levels and preserved the islet morphology in part. LC but not SGLT2i increased body weight accompanied by epididymal fat accumulation. In contrast, SGLT2i, not LC potentiated four-fold ketone production with higher ketogenic gene expression, in comparison with the non-treated Akita mice. Besides, the combination did not enhance further ketone production compared to the SGLT2i alone.ConclusionsOur results indicated that both LC and SGLT2i reduced chronic hyperglycemia, and the combination presented synergistic favorable effects concomitantly with amelioration of islet morphology, while the combination did not enhance further ketosis in Akita mice.

show abstract

Protective effects of the SGLT2 inhibitor luseogliflozin on pancreatic β‐cells in db/db mice: The earlier and longer, the better

Abstract: Luseogliflozin exerts more protective effects in an early stage of diabetes compared to an advanced stage, and longer-term use of luseogliflozin exerts more beneficial effects on pancreatic β-cells compared to short-term use.

Cited by 41 publications

References 66 publications

Investigation of the preservation effect of canagliflozin on pancreatic beta cell mass using SPECT/CT imaging with 111In-labeled exendin-4

Investigation of the preservation effect of canagliflozin on pancreatic beta cell mass using SPECT/CT imaging with 111In-labeled exendin-4

Prospect of Sodium–Glucose Co-transporter 2 Inhibitors Combined With Insulin for the Treatment of Type 2 Diabetes

A Low-Carbohydrate Diet Improves Glucose Metabolism in Lean Insulinopenic Akita Mice Along With Sodium-Glucose Cotransporter 2 Inhibitor

Contact Info

Product

Resources

About