Effect of GLP-1 Treatment on Bone Turnover in Normal, Type 2 Diabetic, and Insulin-Resistant States

The effects of insulin-like growth factor I (IGF-I) and insulin on free fatty acid (FFA) and glucose metabolism were compared in eight control and eight type 2 diabetic subjects, who received a two-step euglycemic hyperinsulinemic (0.25 and 0.5 mU · kg−1 · min−1) clamp and a two-step euglycemic IGF-I (26 and 52 pmol · kg−1 · min−1) clamp with [3-3H]glucose, [1-14C]palmitate, and indirect calorimetry. The insulin and IGF-I infusion rates were chosen to augment glucose disposal (Rd) to a similar extent in control subjects. In type 2 diabetic subjects, stimulation of Rd (second clamp step) in response to both insulin and IGF-I was reduced by ∼40–50% compared with control subjects. In control subjects, insulin was more effective than IGF-I in suppressing endogenous glucose production (EGP) during both clamp steps. In type 2 diabetic subjects, insulin-mediated suppression of EGP was impaired, whereas EGP suppression by IGF-I was similar to that of controls. In both control and diabetic subjects, IGF-I-mediated suppression of plasma FFA concentration and inhibition of FFA turnover were markedly impaired compared with insulin ( P < 0.01–0.001). During the second IGF-I clamp step, suppression of plasma FFA concentration and FFA turnover was impaired in diabetic vs. control subjects ( P < 0.05–0.01). Conclusions: 1) IGF-I is less effective than insulin in suppressing EGP and FFA turnover; 2) insulin-resistant type 2 diabetic subjects also exhibit IGF-I resistance in skeletal muscle. However, suppression of EGP by IGF-I is not impaired in diabetic individuals, indicating normal hepatic sensitivity to IGF-I.

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Muscle glucose transport and phosphorylation in type 2 diabetic, obese nondiabetic, and genetically predisposed individuals

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00617.2005 ◽

2007 ◽

Vol 292 (1) ◽

pp. E92-E100 ◽

Cited By ~ 48

Author(s):

Merri Pendergrass ◽

Alessandra Bertoldo ◽

Riccardo Bonadonna ◽

Gianluca Nucci ◽

Lawrence Mandarino ◽

...

Keyword(s):

Glucose Transport ◽

Brachial Artery ◽

Glucose Concentration ◽

Whole Body ◽

Insulin Resistant ◽

Normal Glucose ◽

Glucose Phosphorylation ◽

Forearm Muscle ◽

Type 2 Diabetic

Our objectives were to quantitate insulin-stimulated inward glucose transport and glucose phosphorylation in forearm muscle in lean and obese nondiabetic subjects, in lean and obese type 2 diabetic (T2DM) subjects, and in normal glucose-tolerant, insulin-resistant offspring of two T2DM parents. Subjects received a euglycemic insulin (40 mU·m−2·min−1) clamp with brachial artery/deep forearm vein catheterization. After 120 min of hyperinsulinemia, a bolus of d-mannitol/3- O-methyl-d-[14C]glucose/d-[3-3H]glucose (triple-tracer technique) was given into brachial artery and deep vein samples obtained every 12–30 s for 15 min. Insulin-stimulated forearm glucose uptake (FGU) and whole body glucose metabolism (M) were reduced by 40–50% in obese nondiabetic, lean T2DM, and obese T2DM subjects (all P < 0.01); in offspring, the reduction in FGU and M was ∼30% ( P < 0.05). Inward glucose transport and glucose phosphorylation were decreased by ∼40–50% ( P < 0.01) in obese nondiabetic and T2DM groups and closely paralleled the decrease in FGU. The intracellular glucose concentration in the space accessible to glucose was significantly greater in obese nondiabetic, lean T2DM, obese T2DM, and offspring compared with lean controls. We conclude that 1) obese nondiabetic, lean T2DM, and offspring manifest moderate-to-severe muscle insulin resistance (FGU and M) and decreased insulin-stimulated glucose transport and glucose phosphorylation in forearm muscle; these defects in insulin action are not further reduced by the combination of obesity plus T2DM; and 2) the increase in intracelullar glucose concentration under hyperinsulinemic euglycemic conditions in obese and T2DM groups suggests that the defect in glucose phosphorylation exceeds the defect in glucose transport.

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Evaluation of the antidiabetic activity of hydrolyzed peptides derived fromJuglans mandshuricaMaxim. fruits in insulin-resistant HepG2 cells and type 2 diabetic mice

Journal of Food Biochemistry ◽

10.1111/jfbc.12518 ◽

2018 ◽

Vol 42 (3) ◽

pp. e12518 ◽

Cited By ~ 11

Author(s):

Ji Wang ◽

Kaiying Du ◽

Li Fang ◽

Chunlei Liu ◽

Weihong Min ◽

...

Keyword(s):

Hepg2 Cells ◽

Antidiabetic Activity ◽

Diabetic Mice ◽

Insulin Resistant ◽

Type 2 Diabetic

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Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-019-0499-6 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Amirhosein Khoshi ◽

Golnaz Goodarzi ◽

Rezvan Mohammadi ◽

Roghaye Arezumand ◽

Meysam Moghbeli ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Glucose Uptake ◽

Alpha Synuclein ◽

C2c12 Cells ◽

Diabetic Mice ◽

Insulin Metabolism ◽

Insulin Resistant ◽

Type 2 Diabetic

Abstract Background Alpha-synuclein (SNCA) as the presynaptic protein is expressed in different tissues and prevents insulin-resistance (IR) through increasing glucose-uptake by adipocytes and muscles. However, the effect of insulin metabolism on SNCA expression has scarcely elucidated. In present study we assessed the probable effect of insulin resistance on SNCA expression in muscle C2C12 cells and also skeletal muscle tissues of type 2 diabetic mice. Materials and methods Sixteen male C57BL/6 mice were divided into two experimental groups, including control and type 2 diabetic mice with IR (induced by high-fat diet + low-dose streptozotocin). The animals of the study involved the measurements of fasting blood glucose, oral-glucose-tolerance-test, as well as fasting plasma insulin. Moreover, insulin-resistant and insulin-sensitive muscle C2C12 cells were prepared. The insulin-resistance was confirmed by the glucose-uptake assay. Comparative quantitative real time PCR was used to assess the SNCA expression. Results The obtained results have showed a significant ~ 27% decrease in SNCA expression level in muscle tissue of diabetic mice (P = 0.022). Moreover, there was a significant change of SNCA expression in insulin-resistant C2C12 cells (P < 0.001). Conclusion Type 2 diabetes due to insulin-resistance can decrease SNCA gene expression in muscles. In addition to the role of SNCA in cell susceptibility to insulin and glucose uptake, the SNCA expression can also be affected by insulin metabolism.

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Effects of low-intensity pulsed electromagnetic fields on bone microarchitecture, mechanical strength and bone turnover in type 2 diabetic db/db mice

Scientific Reports ◽

10.1038/s41598-017-11090-7 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 10

Author(s):

Jianjun Li ◽

Zhaobin Zeng ◽

Yantao Zhao ◽

Da Jing ◽

Chuhua Tang ◽

...

Keyword(s):

Bone Turnover ◽

Mechanical Strength ◽

Electromagnetic Fields ◽

Bone Microarchitecture ◽

Pulsed Electromagnetic Fields ◽

Low Intensity ◽

Pulsed Electromagnetic ◽

Type 2 Diabetic

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Effect of Troglitazone on the Excess Testosterone and LH Secretion in Thyroidectomized, Insulin-Resistant, Type 2 Diabetic Goto–Kakizaki Rats

Endocrine ◽

10.1385/endo:27:3:301 ◽

2005 ◽

Vol 27 (3) ◽

pp. 301-306 ◽

Cited By ~ 8

Author(s):

Mayumi Matsushita ◽

Kazuhiro Tamura ◽

Shingo Osada ◽

Hiroshi Kogo

Keyword(s):

Insulin Resistant ◽

Lh Secretion ◽

Type 2 Diabetic

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Impaired brown adipose tissue is differentially modulated in insulin-resistant obese wistar and type 2 diabetic Goto-Kakizaki rats

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.112019 ◽

2021 ◽

Vol 142 ◽

pp. 112019

Author(s):

Tamires Duarte Afonso Serdan ◽

Laureane Nunes Masi ◽

Joice Naiara Bertaglia Pereira ◽

Luiz Eduardo Rodrigues ◽

Amanda Lins Alecrim ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Insulin Resistant ◽

Brown Adipose ◽

Type 2 Diabetic

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Increased collagen content in insulin-resistant skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00202.2005 ◽

2006 ◽

Vol 290 (3) ◽

pp. E560-E565 ◽

Cited By ~ 86

Author(s):

Rachele Berria ◽

Lishan Wang ◽

Dawn K. Richardson ◽

Jean Finlayson ◽

Renata Belfort ◽

...

Keyword(s):

Skeletal Muscle ◽

Extracellular Matrix ◽

Collagen Content ◽

Matrix Composition ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Insulin Resistant ◽

Obese Subjects ◽

Type 2 Diabetic

Oversupply and underutilization of lipid fuels are widely recognized to be strongly associated with insulin resistance in skeletal muscle. Recent attention has focused on the mechanisms underlying this effect, and defects in mitochondrial function have emerged as a potential player in this scheme. Because evidence indicates that lipid oversupply can produce abnormalities in extracellular matrix composition and matrix changes can affect the function of mitochondria, the present study was undertaken to determine whether muscle from insulin-resistant, nondiabetic obese subjects and patients with type 2 diabetes mellitus had increased collagen content. Compared with lean control subjects, obese and type 2 diabetic subjects had reduced muscle glucose uptake ( P < 0.01) and decreased insulin stimulation of tyrosine phosphorylation of insulin receptor substrate-1 and its ability to associate with phosphatidylinositol 3-kinase ( P < 0.01 and P < 0.05). Because it was assayed by total hydroxyproline content, collagen abundance was increased in muscle from not only type 2 diabetic patients but also nondiabetic obese subjects (0.26 ± 0.05, 0.57 ± 0.18, and 0.67 ± 0.20 μg/mg muscle wet wt, lean controls, obese nondiabetics, and type 2 diabetics, respectively), indicating that hyperglycemia itself could not be responsible for this effect. Immunofluorescence staining of muscle biopsies indicated that there was increased abundance of types I and III collagen. We conclude that changes in the composition of the extracellular matrix are a general characteristic of insulin-resistant muscle.

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