Metformin Enhances B Cell Function and Antibody Responses of Elderly Individuals With Type-2 Diabetes Mellitus

Our previous work has shown that young and elderly patients with Type-2 Diabetes Mellitus (T2DM) treated with Metformin have optimal B cell function and serum antibodies specific for the seasonal influenza vaccine. In this paper, we have evaluated B cell function and the metabolic requirements of B cell antibody responses in elderly T2DM patients (ET2DM) taking or not Metformin, and compared to those of healthy elderly (EH) and healthy young (YH) individuals. Results show that Metformin significantly increases in vivo B cell function, measured by influenza vaccine-specific serum antibodies, in ET2DM patients to the levels observed in EH and more importantly in YH individuals. Metformin also decreases the frequencies of pro-inflammatory B cell subsets, as well as intrinsic inflammation and metabolic requirements of peripheral B cells from ET2DM. This hyper-metabolic phenotype of B cells from ET2DM is needed to support intrinsic inflammation, measured by the expression of transcripts for markers of the senescence-associated secretory phenotype (SASP), and the secretion of autoimmune antibodies. Importantly, B cell function in ET2DM patients taking Metformin is not only increased as compared to that in ET2DM patients not taking Metformin, but is comparable to B cell function measured in YH individuals. These results altogether strongly support the anti-aging effects of Metformin on humoral immunity.

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Effect of Troglitazone on B Cell Function, Insulin Sensitivity, and Glycemic Control in Subjects with Type 2 Diabetes Mellitus

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.83.3.819 ◽

1998 ◽

Vol 83 (3) ◽

pp. 819-823 ◽

Cited By ~ 29

Author(s):

R. L. Prigeon

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Sensitivity ◽

Glycemic Control ◽

B Cell ◽

Cell Function ◽

B Cell Function

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Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus

Diabetic Medicine ◽

10.1111/j.1464-5491.2007.02333.x ◽

2008 ◽

Vol 25 (2) ◽

pp. 152-156 ◽

Cited By ~ 150

Author(s):

T. Vilsbøll ◽

B. Brock ◽

H. Perrild ◽

K. Levin ◽

H.-H. Lervang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Secretion ◽

B Cell ◽

Cell Function ◽

Once Daily ◽

Pancreatic B Cell ◽

B Cell Function

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Natural History of Pancreatic Islet B-Cell Function in Type 2 Diabetes Mellitus Studied over Six Years by Homeostasis Model Assessment

Diabetic Medicine ◽

10.1111/j.1464-5491.1988.tb00938.x ◽

1988 ◽

Vol 5 (1) ◽

pp. 36-41 ◽

Cited By ~ 51

Author(s):

A. S. Rudenski ◽

D. R. Hadden ◽

A. B. Atkinson ◽

L. Kennedy ◽

D. R. Matthews ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Natural History ◽

Cell Function ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

B Cell Function ◽

History Of

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Ten-year Follow-up of Sitagliptin Treatment in Type 2 Diabetes Mellitus Patients

10.21203/rs.3.rs-855957/v1 ◽

2021 ◽

Author(s):

Sachiko Hattori

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cell Function ◽

Urinary Albumin ◽

Control Group ◽

Glucose Lowering ◽

B Cell Function ◽

History Of

Abstract Background: Early and effective intervention with a dipeptidyl peptidase 4 inhibitor (DPP4i) before the development of advanced atherosclerosis in type 2 diabetes mellitus (T2DM) patients without a history of cardiovascular disease (CVD) is reported to increase the chance of significant reductions in not only microvascular disease, but also CVD. Method: This study aimed to investigate whether sitagliptin is effective and tolerated for glycemic control and whether renoprotective effects and b-cell function are preserved for as long as ten years in Japanese patients with T2DM without a history of CVD. Results: The situation is equivalent to improving glycemic control as assessed by hemoglobin A1c both in a sitagliptin group (sitagliptin 50 mg as either monotherapy or combination therapy with other oral glucose-lowering drugs (n=17)) or a control group (placebo as either monotherapy or combination therapy with other glucose-lowering drugs (n=9)), while anti-inflammatory effects as assessed by high-sensitivity C-reactive peptide in the sitagliptin group were superior to those in the control group. In the sitagliptin group, the mean values of urinary albumin excretion measured as urinary albumin-to-creatinine ratio (ACR) were markedly decreased, but no changes in estimated glomerular filtration rate (eGFR) were seen throughout the study. Beta-cell function as evaluated by homeostatic model assessment of b-cell function (HOMA-β) values was reduced at baseline in both groups, improved significantly in the sitagliptin group, and continued unchanged in the control group during the study. Conclusion: This observation suggests that early intervention with sitagliptin in patients with T2DM may have long-lasting renoprotective and islet-protective effects. Trial registration: UMIN Clinical Registry (UMIN000038459). Registered 01November (Retrospectively registered), https://upload.umin.ac.jp/UMIN000038459

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Plasma relaxin concentration is related to beta-cell function and insulin sensitivity in women with type 2 diabetes mellitus

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2007.10.017 ◽

2008 ◽

Vol 79 (3) ◽

pp. e1-e3 ◽

Cited By ~ 13

Author(s):

Barbara Szepietowska ◽

Maria Gorska ◽

Malgorzata Szelachowska

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Insulin Sensitivity ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function

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Inflammation of adipose tissue. Part 2. Pathogenetic role in type 2 diabetes mellitus

Problems of Endocrinology ◽

10.14341/probl200955543-48 ◽

2009 ◽

Vol 55 (5) ◽

pp. 43-48 ◽

Cited By ~ 3

Author(s):

V Shvarts

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Adipose Tissue ◽

Cell Function ◽

Signal Pathway ◽

Insulin Signal ◽

Kinase Cascade

This review deals with the role of adipose tissue inflammation (ATI) in the development of type 2 diabetes mellitus (DM2). ATI is regarded as a link between obesity and DM2. The review illustrates the involvement of main adipokines in pathogenesis of DM2 and provides a detailed description of such factors as impaired adiponectin and stimulation of cytokine production responsible for metabolic disorders, activation of lipolysis, in adipocytes, increased fatty acid and triglyceride levels, suppression of insulin activity at the receptor and intracellular levels. Adipokines, in the first place cytokines, act on the insulin signal pathway and affect the intracellular inflammatory kinase cascade. At the intercellular level, ATI stimulates JNK and IKK-beta/kB responsible for the development of insulin resistance via such mechanisms as activation of cytokine secretion in the adipose tissue, oxidative stress, and induction of endoplasmic reticulum enzymes. The key role of JNK and IKK-beta/kB in the inhibition of the insulin signal pathway is mediated through inactivation of insulin receptor substrate 1. Also, it is shown that ATI modulates B-cell function and promotes progressive reduction of insulin secretion.

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