459-P: Liver-Targeted Mitochondrial Uncoupling by CRMP Improves Whole-Body Insulin Sensitivity and Attenuates Atherosclerosis in A LDLR-/- Mouse Model of Metabolic Syndrome

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 459-P
Author(s):  
LEIGH GOEDEKE ◽  
NOEMI ROTLLAN ◽  
KESHIA TOUSSAINT ◽  
ALI NASIRI ◽  
XINBO ZHANG ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Mouse Model ◽  
Whole Body ◽  
Mitochondrial Uncoupling

scholarly journals Elevated GH/IGF-I, Due to Somatotrope-Specific Loss of Both IGF-I and Insulin Receptors, Alters Glucose Homeostasis and Insulin Sensitivity in a Diet-Dependent Manner

Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4825-4837 ◽  
Author(s):  
Manuel D. Gahete ◽  
José Córdoba-Chacón ◽  
Chike V. Anadumaka ◽  
Qing Lin ◽  
Jens C. Brüning ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Mouse Model ◽  
Caloric Intake ◽  
Insulin Receptors ◽  
Tumor Formation ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Dependent Manner ◽  
Hepatic Lipid Accumulation ◽  
Igf I

A unique mouse model was developed with elevated endogenous GH (2- to 3-fold) and IGF-I (1.2- to 1.4-fold), due to somatotrope-specific Cre-mediated inactivation of IGF-I receptor (IgfIr) and insulin receptor (Insr) genes (IgfIr,InsrrGHpCre, referred to as HiGH mice). We demonstrate that the metabolic phenotype of HiGH mice is diet dependent and differs from that observed in other mouse models of GH excess due to ectopic heterologous transgene expression or pituitary tumor formation. Elevated endogenous GH promotes lean mass and whole-body lipid oxidation but has minimal effects on adiposity, even in response to diet-induced obesity. When caloric intake is moderated, elevated GH improves glucose clearance, despite low/normal insulin sensitivity, which may be explained in part by enhanced IGF-I and insulin output. However, when caloric intake is in excess, elevated GH promotes hepatic lipid accumulation, insulin resistance, hyperglycemia, and ketosis. The HiGH mouse model represents a useful tool to study the role endogenous circulating GH levels play in regulating health and disease.

Antisense oligonucleotides against the lipid phosphatase SHIP2 improve muscle insulin sensitivity in a dietary rat model of the metabolic syndrome

2007 ◽  
Vol 292 (6) ◽  
pp. E1871-E1878 ◽  
Author(s):  
Roland Buettner ◽  
Iris Ottinger ◽  
Christiane Gerhardt-Salbert ◽  
Christian E. Wrede ◽  
Jürgen Schölmerich ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Protein Content ◽  
Insulin Action ◽  
Whole Body ◽  
Glucose Disposal ◽  
Standard Diet ◽  
The Metabolic Syndrome ◽  
Lipid Phosphatase

The lipid phosphatase SH2 domain-containing lipid phosphatase (SHIP2) has been implicated in the regulation of insulin sensitivity, but its role in the therapy of insulin-resistant states remains to be defined. Here, we examined the effects of an antisense oligonucleotide (AS) therapy directed against SHIP2 on whole body insulin sensitivity and insulin action in liver and muscle tissue in a dietary rodent model of the metabolic syndrome, the high-fat-fed (HF) rat. Whole body insulin sensitivity was examined in vivo by insulin tolerance tests before and after the intraperitoneal application of an AS directed against SHIP2 (HF-SHIP2-AS) or a control AS (HF-Con-AS) in HF rats. Insulin action in liver and muscle was assayed by measuring the activation of protein kinase B (Akt) and insulin receptor substrate (IRS)-1/2 after a portal venous insulin bolus. SHIP2 mRNA and protein content were quantified in these tissues by real-time PCR and immunoblotting, respectively. In HF-SHIP2-AS, whole body glucose disposal after an insulin bolus was markedly elevated compared with HF-Con-AS. In liver, insulin activated Akt similarly in both groups. In muscle, insulin did not clearly activate Akt in HF-Con-AS animals, whereas insulin-induced Akt phosphorylation was sustained in SHIP2-AS-treated rats. IRS-1/2 activation did not differ between the experimental groups. SHIP2 mRNA and protein content were markedly reduced only in muscle. In standard diet-fed controls, SHIP2-AS reduced SHIP2 protein levels in liver and muscle, but it had no significant effect on insulin sensitivity. We conclude that treatment with SHIP2-AS can rapidly improve muscle insulin sensitivity in dietary insulin resistance. The long-term feasability of such a strategy should be examined further.

Are Changes in Whole-Body Insulin Sensitivity during Pregnancy Related to Changes in Ectopic Fat Stores?

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1408-P
Author(s):  
KIMBERLY VESCO ◽  
NICOLE E. MARSHALL ◽  
WILLIAM ROONEY ◽  
MICHAEL C. LEO ◽  
ERIC BAETSCHER ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Whole Body ◽  
Ectopic Fat ◽  
Fat Stores

1741-P: Immune Regulation of Postprandial Glycemia and Whole-Body Insulin Sensitivity through Myeloid Production of IL-10

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1741-P
Author(s):  
GOTARO TODA ◽  
KOTARO SOEDA ◽  
NAOKO ARAKAWA ◽  
YUKARI MASUDA ◽  
NAOKI KOBAYASHI ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Immune Regulation ◽  
Whole Body ◽  
Postprandial Glycemia
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