School-of-Life-Sciences-Shandong-University-Qingdao-266237-Shandong-China-Department-of-Rehabilitation-Qilu-Hospital-Cheeloo-College-of-Medicine-Shandong-University-Jinan-250012-Shandong-China-a

Shandong University, Jinan 250012, Shandong, China.School of Life Sciences, Shandong University, Qingdao 266237, Shandong, China.250012, Shandong, China; Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan 250012, Shandong, China.Shandong University, Jinan 250012, Shandong, China; Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan 250012, Shandong, China; Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan 250012, Shandong, China. Electronic address: School of Life Sciences, Shandong University, Qingdao 266237, Shandong, China. BACKGROUND: Males absent on the first (Mof) is implicated in gene control of diverse biological processes, such as cell growth, differentiation, apoptosis and autophagy.

However, glp 1 meds between glucose regulation and Mof-mediated transcription events remains unexplored. We aimed to unravel the role of Mof in glucose regulation by using global and pancreatic α-cell-specific Mof-deficient mice in vivo and α-TC1-6 cell line in vitro.METHODS: We used tamoxifen-induced temporal Mof-deficient mice first to show Mof regulate glucose homeostasis, islet cell proportions and hormone secretion. Then we used α-cell-specific Mof-deficient mice to clarify how α-cell subsets and β-cell mass were regulated and corresponding hormone level alterations. Ultimately, glipizide drug class used small interfering RNA (siRNA) to knockdown Mof in α-TC1-6 and unravel the mechanism regulating α-cell mass and glucagon secretion.RESULTS: Mof was mainly expressed in α-cells. Global Mof deficiency led to lower glucose levels, attributed by decreased α/β-cell ratio and glucagon secretion.

α-cell-specific Mof-deficient mice exhibited similar alterations, with more reduced prohormone convertase 2 (PC2)-positive α-cell mass, responsible for less glucagon, and enhanced prohormone convertase 1 (PC1/3)-positive α-cell mass, leading to more glucagon-like peptide-1 (GLP-1) secretion, thus increased β-cell mass and insulin secretion. In vitro, increased DNA damage, dysregulated autophagy, enhanced apoptosis and altered cell fate factors expressions upon Mof knockdown were observed. Genes and pathways linked to impaired glucagon secretion were uncovered through transcriptome sequencing.CONCLUSION: Mof is a potential interventional target for glucose regulation, from the aspects of both α-cell subset mass and glucagon, intra-islet GLP-1 secretion. Upon Mof deficiency, Up-regulated PC1/3 but down-regulated PC2-positive α-cell mass, leads to more GLP-1 and insulin but less glucagon secretion, and contributed to lower glucose level.Conflict of interest statement: Declaration of competing interest None.β-Cell Sensitivity to GLP-1 in Healthy Humans Is Variable and Proportional to H.

E.W.-P., D.A.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; University of Maryland School of Medicine (R.

L.P.), and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201; and Cincinnati Veterans Affairs Medical Center (D.A.D.), Cincinnati, Ohio 45220.CONTEXT: Glucagon-like peptide-1 (GLP-1) is an insulinotropic factor made in the gastrointestinal tract that is essential for normal glucose tolerance.

Infusion of GLP-1 increases insulin secretion in both diabetic and nondiabetic humans. However, the degree to which people vary in their β-cell sensitivity to GLP-1 and the factors contributing to this variability have not been reported.OBJECTIVE: The objective was to measure the sensitivity of insulin secretion to GLP-1 in cohorts of lean and obese subjects across a broad range of insulin METHODS: Insulin secretion was measured during clamped hyperglycemia (7 mmol/L) and graded GLP-1 infusion in young, healthy subjects, and GLP-1 sensitivity was computed from the insulin secretion rate (ISR) during progressive increases in plasma GLP-1.RESULTS: All subjects had fasting glucose values <5 mm. The obese subjects were insulin resistant compared to the lean group (homeostasis model of assessment 2 for insulin resistance: obese, 2 ± 0; lean, 0 ± 0; P < 01). ISR increased linearly in both cohorts with escalating doses of GLP-1, but the slope of ISR in response to GLP-1 was greater in the obese than in the lean subjects (obese, 07 ± 03 nmol/min/pm; lean, 05 ± 01 nmol/min/pm; P < 01). There was a significant association of β-cell GLP-1 sensitivity and insulin resistance (r = 03; P < 01), and after correction for homeostasis model of assessment 2 for insulin resistance, the slopes of ISR vs GLP-1 concentration did not differ in the two cohorts (obese, 08 ± 01; lean, 08 ± 01; P = 8).

However, within the entire study group, β-cell GLP-1 sensitivity corrected for insulin resistance varied nearly 10-fold.CONCLUSIONS: Insulin secretion in response to GLP-1 is proportional to insulin resistance in healthy subjects. However, there is considerable variability in the sensitivity of the β-cell to GLP-1 that is independent of insulin Effect of GLP-1 and GIP on C-peptide secretion after glucagon or mixed meal tests: Significance in assessing B-cell function in diabetes.