Protein Feeding Promotes Redistribution of Endogenous Glucose Production to the Kidney and Potentiates Its Suppression by Insulin

The aim of this study was to assess in rats the effect of protein feeding on the: 1) distribution of endogenous glucose production (EGP) among gluconeogenic organs, and 2) repercussion on the insulin sensitivity of glucose metabolism. We used gene expression analyses, a combination of glucose tracer dilution and arteriovenous balance to quantify specific organ release, and hyperinsulinemic euglycemic clamps to assess EGP and glucose uptake. Protein feeding promoted a dramatic induction of the main regulatory gluconeogenic genes (glucose-6 phosphatase and phosphoenolpyruvate carboxykinase) in the kidney, but not in the liver. As a consequence, the kidney glucose release was markedly increased, compared with rats fed a normal starch diet. Protein feeding ameliorated the suppression of EGP by insulin and the sparing of glycogen storage in the liver but had no effect on glucose uptake. Combined with the previously reported induction of gluconeogenesis in the small intestine, the present work strongly suggests that a redistribution of glucose production among gluconeogenic organs might occur upon protein feeding. This phenomenon is in keeping with the improvement of insulin sensitivity of EGP, most likely involving the hepatic site. These data shed a new light on the improvement of glucose tolerance, previously observed upon increasing the amount of protein in the diet, in type 2 diabetic patients. Protein feeding increases kidney gluconeogenesis without increasing global endogenous glucose production, and improves insulin suppression of the latter, likely at the hepatic site.

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Type 2 diabetic patients have increased gluconeogenic efficiency to substrate availability, but intact autoregulation of endogenous glucose production

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.1080/00365510510025692 ◽

2005 ◽

Vol 65 (4) ◽

pp. 307-320 ◽

Cited By ~ 6

Author(s):

I. Toft ◽

T. Jenssen

Keyword(s):

Glucose Production ◽

Endogenous Glucose Production ◽

Diabetic Patients ◽

Substrate Availability ◽

Type 2 Diabetic Patients ◽

Endogenous Glucose ◽

Type 2 Diabetic

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-0378 ◽

2009 ◽

Vol 94 (9) ◽

pp. 3297-3305 ◽

Cited By ~ 13

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.

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The Dipeptidyl Peptidase IV Inhibitor Vildagliptin Suppresses Endogenous Glucose Production and Enhances Islet Function after Single-Dose Administration in Type 2 Diabetic Patients

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-1882 ◽

2007 ◽

Vol 92 (4) ◽

pp. 1249-1255 ◽

Cited By ~ 164

Author(s):

Bogdan Balas ◽

Muhammad R. Baig ◽

Catherine Watson ◽

Beth E. Dunning ◽

Monica Ligueros-Saylan ◽

...

Keyword(s):

Single Dose ◽

Glucose Production ◽

Endogenous Glucose Production ◽

Diabetic Patients ◽

Islet Function ◽

Type 2 Diabetic Patients ◽

Dose Administration ◽

Endogenous Glucose ◽

Type 2 Diabetic

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Insulin sensitivity and body composition in cirrhosis: changes after TIPS

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00375.2009 ◽

2010 ◽

Vol 299 (2) ◽

pp. G486-G493 ◽

Cited By ~ 12

Author(s):

Peter Holland-Fischer ◽

Michael Festersen Nielsen ◽

Hendrik Vilstrup ◽

Dennis Tønner-Nielsen ◽

Anette Mengel ◽

...

Keyword(s):

Liver Cirrhosis ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Mass ◽

Area Under The Curve ◽

Glucose Production ◽

Endogenous Glucose Production ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Endogenous Glucose

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production. After TIPS, BCM increased by 4.8 kg [confidence interval (CI): 2.7–7.3]. Fasting (f)-insulin increased from 123 ± 81 to 193 ± 124 pmol/l ( P = 0.03), whereas f-glucose was unchanged (6.0 ± 0.8 vs. 6.2 ± 1.0 mmol/l). Glucose and insulin oral glucose tolerance test area under the curve increased by 14% (CI: 7–22%) and 53% (CI: 14–90%), respectively, P < 0.05. The C-peptide-to-insulin ratio decreased by 21% (CI: 8-35%, P = 0.01). Insulin sensitivity based on glucose infusion rate (4.69 ± 1.82 vs. 4.85 ± 2.37 mg·kg−1·min−1) and glucose tracer-based rate of disappearance were unchanged (5.01 ± 1.61 vs. 4.97 ± 2.13 mg·kg−1·min−1). Despite a further increase in peripheral hyperinsulinemia, f-endogenous glucose production did not change between study days (2.01 ± 0.42 vs. 2.42 ± 0.58 mg·kg−1·min−1) and was suppressed equally by insulin (1.1 ± 0.1 vs. 1.0 ± 0.1 mg·kg−1·min−1). Insulin clearance, growth hormone, cortisol, and glucagon levels were unchanged. BCM improvement did not correlate with the measured variables. After TIPS, BCM rose, despite enhanced hyperinsulinemia and aggravated glucose intolerance, but unchanged peripheral and hepatic insulin sensitivity. This apparent discrepancy may be ascribed to shunt-related decreased insulin exposure to the liver cells. However, the anabolic effect of TIPS seems not to be related to improvements in insulin sensitivity and remains mechanistically unexplained.

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