scholarly journals Hypothesis: Role of Reduced Hepatic Insulin Clearance in the Pathogenesis of Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (9) ◽  
pp. 1709-1716 ◽  
Author(s):  
Richard N. Bergman ◽  
Francesca Piccinini ◽  
Morvarid Kabir ◽  
Cathryn M. Kolka ◽  
Marilyn Ader
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Clearance ◽  
Hepatic Insulin Clearance

scholarly journals Erratum. Hypothesis: Role of Reduced Hepatic Insulin Clearance in the Pathogenesis of Type 2 Diabetes. Diabetes 2019;68:1709–1716

Diabetes ◽  
2019 ◽  
Vol 68 (12) ◽  
pp. 2350-2350
Author(s):  
Richard N. Bergman ◽  
Francesca Piccinini ◽  
Morvarid Kabir ◽  
Cathryn M. Kolka ◽  
Marilyn Ader
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Clearance ◽  
Hepatic Insulin Clearance

Reduced Postprandial Hepatic Insulin Clearance via the DPP-4 Inhibitor Anagliptin Contributed to Improvement in Hyperglycemia in Patients with Type 2 Diabetes Mellitus

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1176-P
Author(s):  
YASUHIRO MATSUBAYASHI ◽  
TAKAHIRO ABE ◽  
SAYAKA MURAGISHI ◽  
AKIHIRO YOSHIDA ◽  
HIDEKI SUGANAMI ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Clearance ◽  
Hepatic Insulin Clearance

scholarly journals Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Secretion ◽  
Early Stage ◽  
Insulin Clearance ◽  
Future Research ◽  
Age Related ◽  
Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

scholarly journals The Effect of Sodium-Glucose Cotransporter 2 Inhibitor Ipragliflozin on Insulin Resistance, Hepatic Insulin Clearance, Beta-Cell Function in the Japanese Patients with type 2 Diabetes

2021 ◽  
Author(s):  
Tsuyoshi Okura ◽  
Yohei Fujioka ◽  
Risa Nakamura ◽  
Sonoko Kitao ◽  
Yuichi Ito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Composition ◽  
Beta Cell Function ◽  
Cell Function ◽  
Insulin Clearance ◽  
C Peptide ◽  
Sodium Glucose Cotransporter ◽  
Hepatic Insulin Clearance

Abstract Introduction: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a medication for type 2 diabetes mellitus (T2DM). Some reports showed SGLT2i improved insulin resistance, however, the effect on insulin resistance is not well established. Hepatic insulin clearance (HIC) is new pathophysiology of T2DM. The effect of SGLT2i on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i on insulin resistance, insulin secretion, incretins, body composition, and hepatic insulin clearance. Materials and Methods: We conducted a meal tolerance test (MTT), and the hyperinsulinemic-euglycemic clamp in 9 T2DM patients. 50 mg/day ipragliflozin was admitted, MTT and clamp were performed after 4 months. We calculated the postprandial C-peptide AUC to insulin AUC ratio as the HIC. We also measured GLP1, GIP, and glucagon levels during MTT. Results: Body weight, HbA1c, and body composition were not significantly changed after 4 months of treatment. Postprandial glucose, fasting, and postprandial insulin were significantly decreased. The insulin resistance of the glucose clamp was not changed, but HOMA-IR and insulin sensitivity index (ISI) were significantly improved. Incretins and glucagon were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. Fib 4 index and fatty liver index were significantly reduced. HOMA-beta and insulinogenic index was not changed but the C-peptide index was significantly increased. Conclusions: Although patients’ number was small, these results suggest that SGLT2i treatment decreased hepatic insulin resistance, increased hepatic insulin clearance, and decreased hyperinsulinemia, it might protect beta-cell function.

Hepatic Insulin Clearance Is Increased in the Patients with Poorly Controlled Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1946-P
Author(s):  
TSUYOSHI OKURA ◽  
MARI ANNO ◽  
YUICHI ITO
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Clearance ◽  
Hepatic Insulin Clearance

scholarly journals Hepatic insulin clearance is increased in patients with high HbA1c type 2 diabetes: a preliminary report

2020 ◽  
Vol 8 (1) ◽  
pp. e001149 ◽  
Author(s):  
Tsuyoshi Okura ◽  
Yohei Fujioka ◽  
Risa Nakamura ◽  
Mari Anno ◽  
Yuichi Ito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Gene Polymorphism ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Insulin Clearance ◽  
Model Assessment ◽  
High Hba1c ◽  
Hepatic Insulin Clearance

IntroductionHepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes. HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. However, hyperglycemia was suggested to enhance HIC, and it is not known whether poorly controlled diabetes increases HIC in patients with type 2 diabetes. We investigated whether HIC was increased in patients with poorly controlled diabetes, and whether HIC was associated with insulin resistance and incretins.Research design and methodsWe performed a meal tolerance test and the hyperinsulinemic–euglycemic clamp in 21 patients with type 2 diabetes. We calculated the postprandial C-peptide area under the curve (AUC)-to-insulin AUC ratio as the HIC; measured fasting and postprandial glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon levels and analyzed serum adiponectin and zinc transporter-8 (ZnT8) gene polymorphism.ResultsThe HIC significantly correlated with glycated hemoglobin (HbA1c) (r_S=0.58, p<0.01). In patients with high HIC above the median of 6.5, the mean HbA1c was significantly higher compared with low HIC below the median. Homeostatic model assessment (HOMA)-beta (r_S=−0.77, p<0.01) and HOMA-IR (r_S=−0.66, p<0.005) were correlated with HIC. The M/I value in the clamp study was correlated with HIC. GLP-1-AUC and GIP-AUC were not correlated with HIC. Glucagon-AUC was negatively correlated with HIC, but there were no significant differences between the high and low HIC groups. Adiponectin was positively correlated with HIC. The ZnT8 gene polymorphism did not affect HIC.ConclusionsThese results suggest that HIC was increased in patients with high HbA1c type 2 diabetes, low insulin secretion, low insulin resistance and high adiponectin conditions.

The role of oncostatin m in the development of type 2 diabetes associated with obesity

2018 ◽  
Author(s):  
Siri Taxeras ◽  
Irene Piquer-Garcia ◽  
Silvia Pellitero ◽  
Rocio Puig ◽  
Eva Martinez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Oncostatin M
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