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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total <t>cholesterol</t> (TC) levels ( n = 3). (H) The high-density <t>lipoprotein</t> cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.
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The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total cholesterol (TC) levels ( n = 3). (H) The high-density lipoprotein cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.

Journal: Journal of Pharmaceutical Analysis

Article Title: Metabolomics-driven elucidation of the synergistic therapeutic mechanism of a novel SGLT-2/PPAR-γ dual receptor supramolecular system for treatment diabetes and obesity

doi: 10.1016/j.jpha.2025.101308

Figure Lengend Snippet: The normal diet (ND)-wild-type (WT) group, high-fat diet (HFD)-WT diabetic mice group (MOD), and HFD-induced diabetic mice treated with either dapagliflozin (DAP), pioglitazone (PIO), a physical mixture (PM), or co-amorphous (COA-I) exhibited varying effects on glucose (GLU) homeostasis and insulin resistance. (A) The scheme for the establishment and treatment of the HFD-induced diabetic mice model. (B) The blood GLU curve of oral glucose tolerance test (OGTT). ( n = 6). (C) The area under the curve (AUC) for GLU in OGTT ( n = 6). (D) The blood GLU curve of insulin tolerance test (ITT) ( n = 6). (E) AUC for GLU in ITT ( n = 6). (F) The serum triglyceride (TRIG) levels ( n = 3). (G) The total cholesterol (TC) levels ( n = 3). (H) The high-density lipoprotein cholesterol (HDL-C) levels ( n = 3). (I) The low-density lipoprotein cholesterol (LDL-C) levels ( n = 3). (J) Serum quantification of alanine aminotransferase (ALT) ( n = 3). (K) Serum quantification of aspartate aminotransferase (AST) ( n = 3). (L) The serum fasting insulin levels (FINS) ( n = 3). (M) Homeostasis model assessment-insulin resistance (HOMA-IR) index ( n = 3). (N) Hematoxylin and eosin (H&E) of the pancreatic sections. (O) Immunohistochemistry staining for insulin (shown in tan). (P) Immunofluorescence staining of insulin (shown in green fluorescence). Data are mean ± standard deviations (SD). Significance levels were denoted as follows: ∗ P < 0.05, ∗∗ P < 0.01, and ∗∗∗ P < 0.001, with these values indicating statistical significance.

Article Snippet: Other chemicals, such as total cholesterol (TC) content determination kit, triglycerides (TRIG) content determination kit, high-density lipoprotein cholesterol (HDL-C) determination kit, LDL-C determination kit, alanine aminotransferase (ALT) determination kit, and aspartate aminotransferase (AST) determination kit were acquired from Jiangsu Jingmei Biotechnology Co., Ltd. (Yancheng, Jiangsu, China).

Techniques: Immunohistochemistry, Staining, Immunofluorescence, Fluorescence