scholarly journals Recombinant Human Insulin-Like Growth Factor I Treatment for 1 Week Improves Metabolic Control in Type 2 Diabetes by Ameliorating Hepatic and Muscle Insulin Resistance*

2000 ◽  
Vol 85 (9) ◽  
pp. 3077-3084
Author(s):  
Kenneth Cusi ◽  
Ralph DeFronzo
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Growth Factor ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Recombinant Human Insulin ◽  
Factor I ◽  
Endogenous Glucose

Abstract The administration of recombinant human insulin-like growth factor I (rhIGF-I) reduces hyperglycemia and insulin requirements in subjects with severe insulin resistance syndromes and in patients with type 2 diabetes mellitus (T2DM). However, the mechanisms responsible for the improved metabolic control are incompletely understood. One proposed mechanism is that rhIGF-I therapy in T2DM may bypass early defects in insulin action (i.e. signal transduction), leading to improved hepatic and/or peripheral insulin sensitivity. To test this hypothesis, we used the euglycemic insulin clamp to measure the response to 7 days of rhIGF-I therapy (80 μg/kg, sc, twice daily) in eight poorly controlled T2DM subjects. rhIGF-I significantly improved fasting (203 ± 12 vs. 134 ± 14 mg/dL; P < 0.01) and day-long (0800–1700 h; 234 ± 11 vs. 153 ± 10 mg/dL; P < 0.01) plasma glucose levels. Basal endogenous glucose production decreased from 3.2 ± 0.2 to 2.7 ± 0.2 mg/kg lean body mass· min (P < 0.03) despite a concomitant decline in the fasting plasma insulin concentration from 13 ± 5 to 5 ± 1 μU/mL (P < 0.01). The decrement in basal endogenous glucose production was closely correlated with the decrement in fasting plasma glucose concentration (r = 0.78; P < 0.01). Whole body insulin-stimulated glucose disposal increased by 27% (from 5.6 ± 0.8 to 7.1 ± 0.8 mg/kg lean body mass·min; P < 0.01), but remained well below that observed in age- and weight-matched healthy subjects. The effects of rhIGF-I on endogenous glucose production and peripheral insulin sensitivity resemble those observed with intensified insulin regimens in T2DM. We conclude that 7 days of sc rhIGF-I improves glucose control by improving hepatic and muscle insulin sensitivity, but it remains markedly abnormal. This indicates that an intrinsic defect(s) responsible for insulin resistance in T2DM cannot be overcome by rhIGF-I treatment.

scholarly journals Recombinant Human Insulin-Like Growth Factor-I Treatment Inhibits Gluconeogenesis in a Transgenic Mouse Model of Type 2 Diabetes Mellitus

Endocrinology ◽  
2006 ◽  
Vol 147 (6) ◽  
pp. 2619-2630 ◽  
Author(s):  
Patricia Pennisi ◽  
Oksana Gavrilova ◽  
Jennifer Setser-Portas ◽  
William Jou ◽  
Stefania Santopietro ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Growth Factor ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Recombinant Human Insulin ◽  
Factor I

Effect of Glucagon on Nocturnal Rates of Endogenous Glucose Production in Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 44-OR
Author(s):  
ANANDA BASU ◽  
HUALING ZHAI ◽  
RICKEY CARTER ◽  
RITA BASU
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Endogenous Glucose

scholarly journals Effects of Growth Hormone and Free Fatty Acids on Insulin Sensitivity in Patients with Type 1 Diabetes

2009 ◽  
Vol 94 (9) ◽  
pp. 3297-3305 ◽  
Author(s):  
Burak Salgin ◽  
Maria L. Marcovecchio ◽  
Rachel M. Williams ◽  
Sarah J. Jackson ◽  
Leslie J. Bluck ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Growth Hormone ◽  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Endogenous Glucose

Context: Because GH stimulates lipolysis, an increase in circulating free fatty acid levels, as opposed to a direct effect of high GH levels, could underlie the development of insulin resistance in type 1 diabetes (T1D). Our aim was to explore the relative contributions of GH and free fatty acids to the development of insulin resistance in patients with T1D. Patients: Seven (four females, three males) nonobese patients with T1D aged 21–30 yr were studied on four occasions in random order. On each visit, overnight endogenous GH production was suppressed by octreotide. Three 1-h pulses of recombinant human GH (rhGH) or placebo were administered on two visits each. Acipimox, an antilipolytic drug, or a placebo were ingested every 4 h on two visits each. Stable glucose and glycerol isotopes were used to assess glucose and glycerol turnover. The overnight protocol was concluded by a two-step hyperinsulinemic euglycemic clamp on each visit. Main Outcome: rhGH administration led to increases in the insulin infusion rate required to maintain euglycemia overnight (P = 0.008), elevated basal endogenous glucose production (P = 0.007), decreased basal peripheral glucose uptake (P = 0.03), and reduced glucose uptake during step 1 of the clamp (P < 0.0001). Coadministration of rhGH and acipimox reversed these effects and suppression of lipolysis in the absence of GH replacement led to further increases in insulin sensitivity. Results: GH pulses were associated with an increase in endogenous glucose production and decreased rates of peripheral glucose uptake, which was entirely reversed by acipimox. Therefore, GH-driven decreases in insulin sensitivity are mainly determined by the effect of GH on lipolysis. Growth hormone decreases insulin sensitivity through increases in free fatty acid levels.

Impaired suppression of endogenous glucose production in lean Japanese patients with type 2 diabetes mellitus

2011 ◽  
Vol 93 (1) ◽  
pp. e1-e2 ◽  
Author(s):  
Mitsuyoshi Takahara ◽  
Hideaki Kaneto ◽  
Naoto Katakami ◽  
Taka-aki Matsuoka ◽  
Munehide Matsuhisa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Production ◽  
Japanese Patients ◽  
Endogenous Glucose Production ◽  
Endogenous Glucose

Resistance training enhances insulin suppression of endogenous glucose production in elderly women

2016 ◽  
Vol 120 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Miikka-Juhani Honka ◽  
Marco Bucci ◽  
Jonathan Andersson ◽  
Ville Huovinen ◽  
Maria Angela Guzzardi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Resistance Training ◽  
Maternal Obesity ◽  
Elderly Women ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Training Intervention ◽  
Ectopic Fat ◽  
Endogenous Glucose

An altered prenatal environment during maternal obesity predisposes offspring to insulin resistance, obesity, and their consequent comorbidities, type 2 diabetes and cardiovascular disease. Telomere shortening and frailty are additional risk factors for these conditions. The aim of this study was to evaluate the effects of resistance training on hepatic metabolism and ectopic fat accumulation. Thirty-five frail elderly women, whose mothers' body mass index (BMI) was known, participated in a 4-mo resistance training program. Endogenous glucose production (EGP) and hepatic and visceral fat glucose uptake were measured during euglycemic hyperinsulinemia with [18F]fluorodeoxyglucose and positron emission tomography. Ectopic fat was measured using magnetic resonance spectroscopy and imaging. We found that the training intervention reduced EGP during insulin stimulation [from 5.4 (interquartile range 3.0, 7.0) to 3.9 (−0.4, 6.1) μmol·kg body wt−1·min−1, P = 0.042] in the whole study group. Importantly, the reduction was higher among those whose EGP was more insulin resistant at baseline (higher than the median) [−5.6 (7.1) vs. 0.1 (5.4) μmol·kg body wt−1·min−1, P = 0.015]. Furthermore, the decrease in EGP was associated with telomere elongation ( r = −0.620, P = 0.001). The resistance training intervention did not change either hepatic or visceral fat glucose uptake or the amounts of ectopic fat. Maternal obesity did not influence the studied measures. In conclusion, resistance training improves suppression of EGP in elderly women. The finding of improved insulin sensitivity of EGP with associated telomere lengthening implies that elderly women can reduce their risk for type 2 diabetes and cardiovascular disease with resistance training.

scholarly journals SAT-653 Exploring the Role of Brown Adipokines on Hepatic Insulin Resistance Using a Microfluidic Organ-On-Chip

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nida Tanataweethum ◽  
Chaeeun Lee ◽  
Allyson Trang ◽  
Franklin Zhong ◽  
Kihwan Kim ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Production ◽  
Conditioned Media ◽  
Hepatic Insulin Resistance ◽  
Brown Adipocyte ◽  
On Chip

Abstract The development of insulin resistance (IR) in liver is a key of pathophysiologic response in type 2 diabetes. Although insulin resistance impairs its ability to suppress hepatic glucose production, insulin regulation of lipogenesis is maintained (1). Currently available insulin sensitizers are effective at lowering glucose levels, but have significant adverse effect on weight gain due to triglyceride accumulation, which highlights a need to develop new therapeutic treatment options for type 2 diabetes. Brown adipose tissue (BAT) has been studied as a new target for anti-obesity and type 2 diabetes as BAT stimulation increases energy expenditure, reduces adiposity, and improves insulin sensitivity (2). However, the underlying mechanisms are not completely understood. To identify the role of BAT adipokines on hepatic insulin resistance, we developed an insulin resistant liver organ-on-chip model and then perfused primary mouse brown adipocyte conditioned media through the hepatocytes. Our results demonstrate that IR hepatocytes treated with brown adipocyte - conditioned media restores insulin sensitivity and improves glucose metabolism. This was verified by significantly increased expression of Phospho-Akt (Ser473) and glucose production gene markers (G6pc and PEPCK), lowered glucose production, increased glucose uptake, and increased glycogen synthesis in treated hepatocytes over IR group (p < 0.05). Our results also indicate that brown adipocyte - conditioned media treatment has the potential to suppress lipogenesis in hepatic insulin resistance. This was confirmed by significantly reduced expression of a lipogenesis gene marker (SREPB1) and fatty acid uptake in treated hepatocytes over IR group (p < 0.05). Current efforts are focused towards identifying the BAT adipokine via mass spectrometry. We conclude that BAT-derived endocrine factors could be a potential target for new drug discovery for obesity and type 2 diabetes treatment. Reference: (1) Langlet et al. Cell. 2017 Nov;171(4):824-835. (2) Subhadraw et al. Am J Physiol Endocrinol Metlab. 2015 Jun;308(12):E1043-E1055. Nothing to Disclose: NT, CL, AT, FZ, KK, JM, RC, AB

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