Research ArticleExperimental Studies
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Effects of a Sodium-Glucose Cotransporter 2 Inhibitor Dapagliflozin on Pancreas in Obese Diabetic Mice

RYOKO SEKIKAWA, HIKARI UEHARA, KINUKO UNO, TOMOHIKO SASASE, YUSUKE NAKATA, YUKINA MORI, MASAMI SHINOHARA, MIKI SUGIMOTO and TAKESHI OHTA
In Vivo January 2026, 40 (1) 650-662; DOI: https://doi.org/10.21873/invivo.14227

Abstract

Background/Aim: Insulin secretion deficiency is one of the factors that cause onset and progression of type 2 diabetes, and pancreatic β-cell mass is also reduced in patients with type 2 diabetes. Some anti-diabetic drugs act directly on the pancreas to promote insulin secretion. Although such drugs provide good glycemic control, there are concerns regarding secondary failure during long-term treatment. Therefore, we aimed to investigate the effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin, which does not act directly on the pancreas, using obese type 2 diabetic mice.

Materials and Methods: Six-week-old db/db mice were administered dapagliflozin at doses equivalent to 0.3 or 1 mg/kg in their diet for nine weeks.

Results: Dapagliflozin treatment increased blood insulin levels and improved hyperglycemia. Histological analysis showed an increase in islet areas and improved islet irregularity and fibrosis in a dose-dependent manner. Immunostaining also showed a dose-dependent increase in β-cell positive areas and decrease in the ratio of α-cell positive area/β-cell positive area. Furthermore, dapagliflozin treatment suppressed the expression of CD44 (an inflammation- and fibrosis-related factor) around the pancreatic islets.

Conclusion: Treatment with dapagliflozin for nine weeks increases insulin secretion and preserves β-cell areas in type 2 diabetic mice, suggesting that long-term administration of dapagliflozin may have a protective effect on pancreas affected by diabetes.

Keywords:

Introduction

In type 2 diabetes, insulin resistance and impaired insulin secretion lead to a relative insulin deficiency, which causes persistent hyperglycemia and leads to development of diabetes. Insulin secretion deficiency is the cause of the onset of type 2 diabetes. In patients with type 2 diabetes, the pancreatic β-cell mass decreases with concomitant dysfunction of insulin secretion. Loss of pancreatic β-cells in type 2 diabetes has been shown to be due to increased apoptosis of β cells (1-3). With progression of diabetes, pancreatic islets exhibit immune cell infiltration, amyloid deposition, and even fibrosis, leading to progressive loss of β cells (4).

Various antidiabetic drugs have been developed, including sulfonylureas (SU drugs), dipeptidyl peptidase (DPP) 4 inhibitors, and glucagon-like peptide (GLP)-1 receptor agonists, which are known insulin secretagogues. SU drugs directly stimulate the SU receptors in pancreatic β cells to promote insulin secretion, but there are also reports that their long-term use reduces responsiveness of β cells to SU drugs and that chronic administration of SU drugs worsens blood glucose control (5, 6). Therefore, there are concerns that drugs that act directly on the pancreas may place a burden on the pancreas or weaken its effects by causing tachyphylaxis. For long-term glycemic control with the use of drugs, it is important that the particular drug has a protective effect on the pancreas and can maintain satisfactory insulin secretion and β-cell mass without exerting direct action on the pancreas. Therefore, we investigated the pancreatic protective effects of dapagliflozin, which do not act directly on the pancreas.

Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers blood glucose levels by inhibiting glucose reabsorption in renal proximal tubules (7). SGLT2 is specifically expressed in proximal tubules, and the direct effect of dapagliflozin is mainly limited to the proximal tubules. It has been reported that patients with type 2 diabetes treated using SGLT2 inhibitors show improved glycemic control, improved insulin resistance, lower blood pressure, lower plasma lipids, and reduced risk of cardiovascular disease (8, 9). Previously, several studies have reported the effects on pancreas in diabetic animals wherein SGLT2 inhibitors such as luseogliflozin and ipragliflozin were administered for approximately two to four weeks (10-12). In our study, we administered dapagliflozin to db/db mice, an obese type 2 diabetes mouse model, for a long duration of nine weeks and examined the pancreatic protective effect through pathological analysis of the pancreas.

A genome-wide association study (eGWAS) has reported that the immune-cell receptor, CD44, is involved in type 2 diabetes (13) and CD44 has also been studied as a marker for liver fibrosis (14, 15). Therefore, we investigated its potential use as a marker of pancreatic fibrosis.

Materials and Methods

Animals and diets. In this study, a total of 20 mice were prepared: five female C57BL/6J mice (CLEA-Japan, Tokyo, Japan) as normal animals and 15 female db/db mice (CLEA-Japan) as diabetic mice. Female C57BL/6J mice at five weeks of age were used as a normal animal group and fed a normal chow (NC) diet (CE-2, 3.4 kcal/g, CLEA-Japan). Female db/db mice at five weeks of age were used and fed a Western diet (14% fat, 25% sucrose and 2% cholesterol, based on percentage of total calories; Quick Fat with 2% cholesterol, 4.06 kcal/g, CLEA-Japan). At six weeks of age, the db/db mice were divided into three groups (n=5); control, dapagliflozin low-dose (DL), and dapagliflozin high-dose (DH). db/db mice in the dapagliflozin treatment group were fed the drug at a 0.0002% or 0.0006% food admixture (approximately 0.3 or 1 mg/kg/day), beginning at six weeks of age. The mice were administered dapagliflozin from 6 to 14 weeks of age. The animals were housed individually in plastic cages in a room that was controlled for temperature (24±2°C), humidity (50±10%), and lighting (10h dark-14h light cycle), and they had free access to water. All the animals were necropsied at 14 weeks of age. All experimental protocols and animals were used in strict compliance with the guidelines of the Kyoto University for animal experimentation.

Measurements of biological parameters. Body weight was measured weekly from 6 to 14 weeks of age, and food intake and water intake were measured weekly from 6 to 12 weeks of age. Blood biochemical parameters, such as plasma glucose, insulin, glucagon, CD44, triglycerides (TG), and total cholesterol (TC) were measured at 14 weeks of age. Blood samples were collected from the abdominal vena cava under anesthesia with isoflurane inhalation. Plasma glucose, TG, and TC levels were measured using the respective product kits (Roche Diagnostics, Tokyo, Japan) and an automatic analyzer (Hitachi). Plasma insulin, glucagon, and CD44 levels were measured using Mouse/Rat Insulin enzyme-linked immunosorbent assay (ELISA) kit (Morinaga Institute of Biological Science, Yokohama, Japan), Glucagon ELISA-10μl kit (Mercodia, Uppsala, Sweden), and CD44 ELISA kit PicoKine® (Boster Biological Technology, Pleasanton, CA, USA), respectively.

Tissue sampling and histopathological/immunohistochemical staining. Dissections of the mice were performed at 14 weeks of age. The animals were euthanized by cervical dislocation after blood sample collection by exsanguination under isoflurane anesthesia. For pathological analysis, the pancreas was fixed in 10% neutral buffered formalin immediately after collection. The tissues were paraffin-embedded using standard techniques and thin sections (4 μm) were obtained. The tissue sections of the pancreas were stained with hematoxylin and eosin (HE) for histopathological evaluation, including morphological analysis of islet cells; Sirius red/fast staining was also performed for pancreatic fibrosis analysis.

Immunohistochemical examination was performed using antibodies against insulin (1:2,000, Cell Signaling Technology, Inc., Danvers, MA, USA), glucagon (ready-to-use, Nichirei Bioscience Inc., Tokyo, Japan), and CD44 (1:100, Cell Signaling Technology, Inc.). The ImmPRESS HRP Horse Anti-Rabbit IgG Polymer Detection Kit (Vector Laboratories Inc., Newark, CA, USA) was used as the secondary antibody, and signals was visualized using StayBlack/HRP (Abcam, Cambridge, UK).

Histopathological analysis of islets and the peri-islet region. To analyze the morphology of islets, images of HE-stained pancreatic sections were obtained using an microscope (BX51, DP50; Olympus, Tokyo, Japan). Pancreatic islets consisting of five or more cells were analyzed using the image analysis software Image J (16). After scaling the micrographs of the islet, area per unit area, islet circularity, and islet compactness were calculated using Image J. Circularity is calculated using the formula; 4π × (area)/(square of perimeter), where 1 indicates a perfect circle and a smaller value indicates an elongated shape. Solidity is calculated as (area)/(area of convex hull), which is used as an index of irregularity and indicates the degree of unevenness of the islets.

The area of pancreatic fibrosis was measured using Image J, Colour Deconvolution 2 Plugin, TurboReg Plugin, and StackReg Plugin (16-18). The degree of fibrosis was measured within the islets and within areas of 15 and 100 μm surrounding the islets. The degree of fibrosis was calculated as follows; (area stained with Sirius Red)/(area stained with Fast Green).

The insulin- or glucagon-immunostained sections were photographed using an optical scanner, and ratio of the insulin- or glucagon-positive area to the islet area was measured using Image J. Regarding CD44 analysis, the ratio of CD44-positive area to the pancreatic islet area and the ratio of CD44-positive area to the 15 μm and 100 μm areas around the pancreatic islet were measured.

Statistical analysis. All values are expressed as the mean±standard deviation. Statistical analysis was performed using EZR software (Jichi Medical University Saitama Medical Center, Saitama, Japan) (19). Comparisons between normal and control groups were performed using the Mann-Whitney U test, and comparisons among control, DL, and DH groups were performed using the Kruskal-Wallis test followed by multiple comparisons using the Steel-Dwass method to examine differences. Statistical significance was set at p<0.05.

Results

Biological parameters. Changes in body weight and food intake are shown in Figure 1. Body weight increased significantly in db/db mice than in C57BL/6J mice during the experimental period; however, no obvious changes were observed after dapagliflozin administration (Figure 1A). Food intake and water intake were significantly higher in db/db mice than in C57BL/6J mice during the experimental period, and food intake was also significantly higher in the DH group than in control group at 7, 8, 10 and 11 weeks of age (Figure 1B and C).

Figure 1.
Figure 1.

Effects on body weight (A), food intake (B) and water intake (C) in db/db mice with chronic administration of dapagliflozin. C57BL/6J mice served as the normal group, and db/db mice were divided into three groups: control, DL, and DH. Data represent means±standard deviation (n=5). *p<0.05, **p<0.01; significant difference between C57BL/6J mice (normal group) and db/db mice (control group). †p<0.05; significant difference between db/db mice (control group) and dapagliflozin-treated groups (DL and DH). DL: Dapagliflozin low-dose; DH: dapagliflozin high-dose.

Changes in blood biochemistry parameters are shown in Figure 2. Control db/db mice showed hyperglycemia, hyperinsulinemia, hyperglucagonemia, and hyperlipidemia. Blood CD44 levels were lower in db/db mice than in C57BL/6J mice (Figure 2E). Dapagliflozin administration resulted in a dose-dependent hypoglycemic effect, significantly increasing blood insulin levels and decreasing blood cholesterol levels in the DH group (Figure 2A, B and G). Blood glucagon level in the DH group was lower than in control db/db mice (control db/db group, 92.8±28.1 pg/ml vs. DH group, 52.9±20.0 pg/ml; p=0.059) (Figure 2C). Blood glucagon/insulin ratio was significantly reduced in db/db mice than in C57BL/6J mice, and the ratio was further reduced in the dapagliflozin-treated group (Figure 2D).

Figure 2.
Figure 2.

Effects on blood biochemistry parameters in db/db mice at 14 weeks of age with chronic administration of dapagliflozin. C57BL/6J mice served as the normal group, and db/db mice were divided into three groups: control, DL, and DH. (A) Glucose, (B) Insulin, (C) Glucagon, (D) Blood glucagon/insulin ratio, (E) CD44, (F) Triglyceride, (G) Total cholesterol. Data represent means+standard deviation (n=5). *p<0.05, **p<0.01; significant difference between C57BL/6J mice (normal group) and db/db mice (control group). †p<0.05; significant difference between db/db mice (control group) and dapagliflozin-treated groups (DL and DH). DL: Dapagliflozin low-dose; DH: dapagliflozin high-dose.

Morphological analysis of islets. Results of morphological analysis of pancreatic islets are shown in Figure 3, and representative photographs of the tissues are shown in Figure 3D. The islet area in control db/db mice tended to be higher than that in C57BL/6J mice (p=0.056), and the area was significantly increased in the DH group (Figure 3A). Islet circularity and solidity in db/db mice were lower than those in C57BL/6J mice, and dapagliflozin treatment improved islet irregularities in db/db mice in a dose-dependent manner (Figure 3B and C).

Figure 3.
Figure 3.

Effects on morphological changes in pancreatic islets of db/db mice at 14 weeks of age with chronic administration of dapagliflozin. C57BL/6J mice served as the normal group, and db/db mice were divided into three groups: control, DL, and DH. (A) islet area per unit area (100,000 pixels), (B) islet circularity, and (C) islet solidity. Representative histological micrographs of pancreatic islets from each group are shown in (D). Data represent means+standard deviation (n=5). **p<0.01; significant difference between C57BL/6J mice (normal group) and db/db mice (control group). †p<0.05; significant difference between db/db mice (control group) and dapagliflozin-treated groups (DL and DH). The p-value between normal group and control group for islet area (A) was 0.056. Scale bar; 200 μm. DL: Dapagliflozin low-dose; DH: dapagliflozin high-dose.

Analysis of pancreatic fibrosis. Results of fibrosis analysis of the islets and the peri-islet region are shown in Figure 4, and representative photographs of the tissues are shown in Figure 4D. Fibrosis in the pancreatic islets of db/db mice was higher than that in C57BL/6J mice, and the extent of fibrosis was lower in mice treated with dapagliflozin (C57BL group, 0.0188±0.01058; db/db group, 0.0663±0.0488; DL group, 0.0157±0.0093; DH group, 0.0112±0.0111) (Figure 4A). Fibrosis surrounding the islets of db/db mice was significantly increased compared to that in C57BL/6J mice, and these values were reduced by administration of dapagliflozin. Fibrosis within an area of 15 μm surrounding the islets was significantly improved in the DH group (Figure 4B).

Figure 4.
Figure 4.

Effects on pancreatic fibrosis in db/db mice at 14 weeks of age with chronic administration of dapagliflozin. C57BL/6J mice served as the normal group, and db/db mice were divided into three groups: control, DL, and DH. Shown as Sirius Red (SR)/Fast Green (FG) ratio. (A) Fibrosis of inner islet, (B) fibrosis of outer islet (15 μm), (C) fibrosis of outer islet (100 μm). Representative histological micrographs of pancreatic fibrosis from each group are shown in (D). White arrows indicate fibrotic areas around the islets. Data represent means+standard deviation (n=5). **p<0.01; significant difference between C57BL/6J mice (normal group) and db/db mice (control group). †p<0.05; significant difference between db/db mice (control group) and dapagliflozin-treated groups (DL and DH). DL: Dapagliflozin low-dose; DH: dapagliflozin high-dose.

Immunohistochemical analysis. Results of measurements of β cell and α cell areas in the islets are shown in Figure 5, and representative photographs of the tissues stained for insulin and glucagon staining are shown in Figure 6. Ratio of the β cell area in control db/db mice was significantly lower than in C57BL/6J mice, and the values in the group treated with dapagliflozin increased in a dose-dependent manner (Figure 5A). No clear changes were observed in the ratio of α-cell area among the groups (Figure 5B); however, ratio of the α-cell/β-cell area was significantly decreased in the DH group (Figure 5C).

Figure 5.
Figure 5.

Effects on β cell and α cell areas in db/db mice at 14 weeks of age with chronic administration of dapagliflozin. C57BL/6J mice served as the normal group, and db/db mice were divided into three groups: control, DL and DH. Ratios of (A) β cell area (insulin-positive area/islet area), (B) α cell area ratio (glucagon-positive area/islet area), and (C) α cell/β cell area are shown. Data represent means+standard deviation (n=5). **p<0.01; significant difference between C57BL/6J mice (normal group) and db/db mice (control group). †p<0.05; significant difference between db/db mice (control group) and dapagliflozin-treated groups (DL and DH). DL: Dapagliflozin low-dose; DH: dapagliflozin high-dose.

Figure 6.
Figure 6.
Figure 6.

Histological micrographs of pancreatic islets at 14 weeks of age in C57BL/6J mice and db/db mice. (A-D) insulin immunostaining, (E-H) glucagon immunostaining. (A, E) C57BL/6J mouse (normal group), (B, F) db/db mouse (control group), (C, G) db/db mouse treated with low-dose of dapagliflozin, (D, H) db/db mouse treated with high-dose of dapagliflozin. Scale bar: 100 μm.

Results of measurements of CD44 positive area in the islets and peri-islet region are shown in Figure 7. CD44 positive area in the islets was significantly increased in the db/db mice compared to that in C57BL/6J mice; however, there was no significant change in the area surrounding the islets. The CD44 positive area within 100 μm surrounding the islets was significantly suppressed in the DH group (Figure 7C).

Figure 7.
Figure 7.

Effects on CD44 area in db/db mice at 14 weeks of age with chronic administration of dapagliflozin. C57BL/6J mice served as the normal group, and db/db mice were divided into three groups: control, DL, and DH. (A) CD44 area ratio of inner islet, (B) CD44 area ratio of outer islet (15 μm), and (C) CD44 area ratio of outer islet (100 μm). Representative histological micrographs of CD44 immunostaining from each group are shown in (D). White arrows indicate CD44-positive areas around the islets. Data represent means+standard deviation (n=5). **p<0.01; significant difference between C57BL/6J mice (normal group) and db/db mice (control group). †p<0.05; significant difference between db/db mice (control group) and dapagliflozin-treated groups (DL and DH). DL: Dapagliflozin low-dose; DH: dapagliflozin high-dose.

Discussion

In this study, we used normal C57BL/6J mice fed the normal diet CE-2 (healthy group) and type 2 diabetic db/db mice fed the Western-style HSFC diet (pathological group) to examine the effects of dapagliflozin on the pancreas in the pathological group. It is well known that a Western-style diet induces meta-inflammation, a state of chronic metabolic inflammation, and causes non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) through development of inflammation and fibrosis in the liver (20, 21). Pancreatic protective effect of dapagliflozin was investigated by focusing on morphological changes in pancreatic islets, intra- and peri-islet fibrosis, and β- and α-cell areas of the islets. In addition, the expression of CD44 within and surrounding the islets was analyzed to investigate its potential as a fibrosis-related factor in the pancreas or as a pancreatic protective factor.

Histological analysis showed an increase in islet area and an improvement in the degree of islet irregularity, circularity, and solidity in the dapagliflozin-treated groups. Analysis of fibrosis also revealed suppression of fibrosis both within and around the islets, suggesting that the improvement in glucose metabolism by the administration of dapagliflozin suppressed inflammation and fibrosis, and improved islet morphology. Glycemic control improves abnormal pancreatic islet morphology (22, 23) and also inhibits the formation of pancreatic lesions including fibrosis by suppressing oxidative stress (24). The islet area tended to increase in db/db mice than in C57BL/6J mice. Previous studies have reported that the islet area gradually increases in db/db mice from 4 to 12 weeks of age (25) and that increased demand for insulin in type 2 diabetes compensates for increases in beta cell mass to control blood glucose levels (26). In the present study, the islet area was further increased in the dapagliflozin-treated group, suggesting an association with increased blood insulin levels.

Immunostaining revealed that the islet β cell area was decreased in db/db mice compared to that of C57BL/6J mice, and the α cell/ β cell ratio also tended to increase. This suggests that β cell dysfunction and apoptosis may have occurred in db/db mice. In addition, α cells were scattered throughout the islets. It is known that in normal mouse islets, β cells are concentrated at the center of the islet surrounded by non β-cells, such as α cells, thus forming a mantle-core structure (27, 28). This suggests that in mice with advanced diabetic pathology, the islet morphology is disrupted by the formation of vacuoles because of β cell apoptosis and inflammatory cell infiltration from the surrounding area, which may affect the distribution of α cells.

Treatment with dapagliflozin showed an increase in β cell area and a decrease in the α cell/β cell ratio. We believe that the blood glucagon/insulin ratio also decreased in response to these histological changes. In the dapagliflozin-treated group, α cells were dispersed to a lesser extent throughout the islets than in the control group and were more likely to remain around the islets. This condition was more prevalent in the DH group. Dapagliflozin regenerates β cells by inducing phenotype conversion in pancreatic endocrine cells in type 2 diabetic mice (29). In the present study, the presence or absence of β cell regeneration was not examined; however, it was observed that administration of dapagliflozin increased the number of β cells per unit area and also expanded the area of the pancreatic islets. In addition, the increase in plasma insulin concentration suggests that dapagliflozin has an inhibitory effect on glucose reabsorption in the proximal tubules and also increases insulin secretion from the islets, thereby reducing plasma glucose concentration. Furthermore, control of hyperglycemia through administration of dapagliflozin reduces the burden on the pancreas, such as β cell apoptosis, inflammation, and oxidative stress, and is thought to suppress deterioration of islet morphology and progression of fibrosis. Administration of dapagliflozin has been reported to maintain pancreatic function and islet morphology in Zucker Diabetic Fatty (ZDF) rats and to have a positive effect on β cells in mouse models of diabetes and insulin resistance (30, 31).

Secondary failure has been reported with long-term administration of drugs that directly act on the pancreas to promote insulin secretion. Secondary failure of sulfonylureas (SU drugs) has been reported with long-term use, with the secondary failure rates of glibenclamide and glipizide being approximately 20% and 25%, respectively (32, 33). The reason for this secondary failure is believed to be pancreatic exhaustion or desensitization; however, the details remain unknown. There is a concern that repeated administration of GPR119 agonists may also result in tachyphylaxis of insulin secretion (34). Hence, SGLT2 inhibitors, which do not act directly on the pancreas, are expected to exert pancreatic protective effects.

Plasma CD44 levels were significantly lower in db/db mice than in C57BL/6J mice, and there were no significant changes in the CD44 levels in the dapagliflozin-treated groups. Previous studies have reported that CD44 levels are increased in the plasma of diabetic patients (35), whereas other studies have reported that adiponectin-mediated promotion of CD44 suppresses diabetic vascular inflammation and reduces plasma CD44 levels in diabetic patients (36). Furthermore, analysis of factors involved in diabetes and its complications using diabetic mice has shown the effects of inflammation-related factors such as lipopolysaccharide, while also suggesting the involvement of factors other than inflammation-related factors (37-39). In the present study, immunohistochemical findings revealed that CD44-positive areas were frequently observed within the pancreatic islets, and the CD44-positive area within the islets was increased in db/db mice than in C57BL/6J mice. It was also observed that the CD44-positive area surrounding the islets was decreased in the DH group. Previous studies have reported that inhibition of hyaluronic acid synthesis and CD44 deletion lower blood glucose levels and maintain β-cell mass (40), and that CD44 knockout reduces inflammatory cell infiltration in adipose tissue, lowers blood glucose levels, and improves insulin resistance (41). In our study, CD44 expression in the pancreatic tissue increased, albeit partially, with an increase in blood glucose levels and inflammation. However, the CD44 expression decreased when blood glucose levels and inflammation were reduced owing to the administration of dapagliflozin.

Conclusion

In conclusion, treatment with dapagliflozin for nine weeks increases insulin secretion and preserves β-cell area along with inhibition of islet fibrosis in type 2 diabetic mice, suggesting that long-term administration of dapagliflozin may have a protective effect on the pancreas in diabetic patients.

Acknowledgements

We would like to thank Mr. Masaaki Handa and Mr. Yoshinobu Doi (CLEA Japan) for providing animal and feed supplies and thank Editage (www.editage.jp) for English language editing.

Footnotes

  • Authors’ Contributions

    Ryoko Sekikawa, Kinuko Uno and Takeshi Ohta were involved in conceptualization of the project. Ryoko Sekikawa, Hikari Uehara, Kinuko Uno, Tomohiko Sasase, Yusuke Nakata, Yukina Mori, Miki Sugimoto and Takeshi Ohta performed the experiments. Ryoko Sekikawa, Kinuko Uno and Masami Shinohara analyzed data. Ryoko Sekikawa and Takeshi Ohta drafted the manuscript. All Authors approved of the final version of the manuscript.

  • Conflicts of Interest

    All Authors have no conflicts of interest in relation to this study.

  • Funding

    This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  • Artificial Intelligence (AI) Disclosure

    No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.

  • Received September 1, 2025.
  • Revision received September 17, 2025.
  • Accepted September 24, 2025.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

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Effects of a Sodium-Glucose Cotransporter 2 Inhibitor Dapagliflozin on Pancreas in Obese Diabetic Mice
RYOKO SEKIKAWA, HIKARI UEHARA, KINUKO UNO, TOMOHIKO SASASE, YUSUKE NAKATA, YUKINA MORI, MASAMI SHINOHARA, MIKI SUGIMOTO, TAKESHI OHTA
In Vivo Jan 2026, 40 (1) 650-662; DOI: 10.21873/invivo.14227
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