Acute hyperaminoacidemia does not suppress insulin-mediated glucose turnover in healthy young men.

Elevated circulating amino acids (AA) concentrations are purported to cause insulin resistance (IR) in humans. To quantify hyperaminoacidemia effects on insulin-mediated glucose turnover in healthy men, we performed 2-stage pancreatic clamps using octreotide with glucagon and growth hormone replacement. In the basal stage, insulin was infused to maintain euglycemia at postabsorptive levels.

Survival of Patients With Short-Bowel Syndrome on Home Parenteral Nutrition: A Prospective Cohort Study.

Background: Survival of patients with short-bowel syndrome (SBS) receiving home parenteral nutrition (HPN) and associated factors have not been reported recently in North America. The objective of this study was to determine the long-term survival of adult patients with SBS as the primary indication for HPN and assess factors that may affect survival by using the Canadian HPN Registry.

Methods: This is a retrospective analysis of prospectively collected data extracted from the HPN registry, prior to approval of teduglutide in Canada.

Glucose and protein metabolic responses to an energy- but not protein- restricted diet in type 2 diabetes.

Aims: To test the effect of energy restriction with maintained protein intake on body composition and on insulin sensitivity of glucose and protein metabolism in adults with type 2 diabetes (T2D).

Materials And Methods: After 3 days of an isoenergetic diet with 1.2 g/kg/d protein, obese adults with T2D (three women, two men) followed a 5-week diet providing 60% of energy requirements with 45% carbohydrate, and with protein maintained at pre-intervention level.

Neurocognitive and Hormonal Correlates of Voluntary Weight Loss in Humans.

Insufficient responses to hypocaloric diets have been attributed to hormonal adaptations that override self-control of food intake. We tested this hypothesis by measuring circulating energy-balance hormones and brain functional magnetic resonance imaging reactivity to food cues in 24 overweight/obese participants before, and 1 and 3 months after starting a calorie restriction diet. Increased activity and functional connectivity in prefrontal regions at month 1 correlated with weight loss at months 1 and 3.

Plasma Amino Acids vs Conventional Predictors of Insulin Resistance Measured by the Hyperinsulinemic Clamp.

Context: Specific plasma amino acid (AA) profiles including elevated postabsorptive branched-chain amino acids (BCAAs) have been associated with insulin resistance (IR), mostly estimated by homeostatic model assessment. This study assessed the associations of postabsorptive AAs with IR directly measured by insulin-mediated glucose disposal and determined the quantitative value of AAs and conventional IR predictors.

Design: Fifty-one healthy, 31 overweight or obese (Ow/Ob), and 52 men and women with type 2 diabetes (T2D) were studied retrospectively.

Academic stress and personality interact to increase the neural response to high-calorie food cues.

Psychosocial stress is associated with an increased intake of palatable foods and weight gain in stress-reactive individuals. Personality traits have been shown to predict stress-reactivity. However, it is not known if personality traits influence brain activity in regions implicated in appetite control during psychosocial stress.

Insulin resistance of protein anabolism accompanies that of glucose metabolism in lean, glucose-tolerant offspring of persons with type 2 diabetes.

Objective: To test whether protein anabolic resistance is an early defect in type 2 diabetes (T2D).

Research Design And Methods: Seven lean, normoglycemic T2D offspring (T2D-O) and eight matched participants without family history (controls; C) underwent a 3-hour hyperinsulinemic (40 mU/m/min), euglycemic (5.5 mmol/L) and isoaminoacidemic clamp.

Adiponectin-SOGA Dissociation in Type 1 Diabetes.

Context: Circulating adiponectin is elevated in human type 1 diabetes (T1D) and nonobese diabetic (NOD) mice without the expected indications of adiponectin action, consistent with tissue resistance.

Objective: Adiponectin stimulates hepatocyte production of the suppressor of glucose from autophagy (SOGA), a protein that inhibits glucose production. We postulated that due to tissue resistance, the elevation of adiponectin in T1D should fail to increase the levels of a surrogate marker for liver SOGA, the circulating C-terminal SOGA fragment.

Effect of 10% dietary protein intake on whole body protein kinetics in type 2 diabetic adults.

Background & Aims: Insulin resistance of protein metabolism occurs in obesity and type 2 diabetes (T2D). Hyperaminoacidemia during a simulated fed steady-state clamp compensates for this resistance. We tested whether decreasing protein intake affects the response to insulin with or without added amino acids, and if this response differs by sex.

Protein and glucose metabolic responses to hyperinsulinemia, hyperglycemia, and hyperaminoacidemia in obese men.

Objective: In insulin-resistant states, resistance of protein anabolism occurs concurrently with that of glucose, but can be compensated for by abundant amino acid (AA) provision. This effect and its mechanism were sought in obesity.

Methods: Pancreatic clamps were performed in 8 lean and 11 obese men, following 5-h postabsorptive, 3-h infusions of octreotide, basal glucagon, and growth hormone, with clamped postprandial-level insulin, glucose, and AA.

Exercise in ZDF rats does not attenuate weight gain, but prevents hyperglycemia concurrent with modulation of amino acid metabolism and AKT/mTOR activation in skeletal muscle.

Purpose: Protein metabolism is altered in obesity, accompanied by elevated plasma amino acids (AA). Previously, we showed that exercise delayed progression to type 2 diabetes in obese ZDF rats with maintenance of β cell function and reduction in hyperglucocorticoidemia. We hypothesized that exercise would correct the abnormalities we found in circulating AA and other indices of skeletal muscle protein metabolism.

Adiponectin signaling in the liver.

High glucose production contributes to fed and fasted hyperglycemia in Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). The breakdown of the adiponectin signaling pathway in T1D and the reduction of circulating adiponectin in T2D contribute to this abnormal increase in glucose production. Sufficient amounts of insulin could compensate for the loss of adiponectin signaling in T1D and T2D and reduce hyperglycemia.

Maintaining adequate nutrition, not probiotic administration, prevents growth stunting and maintains skeletal muscle protein synthesis rates in a piglet model of colitis.

Malnutrition and cytokine-induced catabolism are pervasive in children with inflammatory bowel diseases (IBD), however, the benefits of aggressive nutrition support or of probiotics on nutrient and functional deficiencies and growth remain unclear. Piglets with dextran sulfate (DS)-induced colitis consuming a 50% macronutrient restricted diet (C-MR) were compared with those receiving probiotics (C-MRP) or adequate nutrition (C-WN) and with healthy well-nourished controls (REF). C-WN versus REF had reduced growth (-34% chest circumference and -22% snout-to-rump length gain) and a tendency toward lesser weight gain, but no differences in skeletal muscle protein fractional synthesis rates (FSR) or initiation of translation via the mTOR pathway were observed.

Anticatabolic effects of avoiding preoperative fasting by intravenous hypocaloric nutrition: a randomized clinical trial.

Objective: We tested the hypothesis that the avoidance of preoperative fasting by hypocaloric nutrition attenuates protein catabolism after surgery.

Summary Background Data: Prolonged fasting before major abdominal procedures has been demonstrated to accentuate the catabolic response to surgery.

Methods: Twenty-two patients undergoing colorectal cancer surgery were randomly assigned to receive glucose and amino acids intravenously starting either 20 hours before the operation or with surgical skin incision.

Fed-state clamp stimulates cellular mechanisms of muscle protein anabolism and modulates glucose disposal in normal men.

Since maximum anabolism occurs postprandially, we developed a simulated fed state with clamped hyperinsulinemia, physiological hyperglycemia, and hyperaminoacidemia (Hyper-3) and explored muscle cellular mechanisms. Whole body [1-(13)C]leucine and [3-(3)H]glucose kinetics in healthy men were compared between hyperinsulinemic, euglycemic, isoaminoacidemic (Hyper-1, n = 10) and Hyper-3 (n = 9) clamps. In Hyper-3 vs.

Malignant transformation of a solitary fibrous tumor of the liver and intractable hypoglycemia.

Sarcomas of the liver are rare. We report a case of intractable hypoglycemia secondary to a solitary fibrous tumor that underwent malignant transformation into a fibrosarcoma. A 70-year-old man presented with a hepatic mass and tumor-associated hypoglycemia which was resistant to medical management.

Insulin resistance of protein metabolism in type 2 diabetes.

Objective: We previously demonstrated that 1) obesity impairs and 2) sex influences insulin sensitivity of protein metabolism, while 3) poor glycemic control in type 2 diabetes accelerates protein turnover in daily fed-fasted states. We hypothesized that type 2 diabetes alters the insulin sensitivity of protein metabolism and that sex modulates it.

Research Design And Methods: Hyperinsulinemic ( approximately 570 pmol/l), euglycemic (5.

Determinants of whole-body protein metabolism in subjects with and without type 2 diabetes.

Objective: Whole-body protein metabolism is abnormal in suboptimally controlled type 2 diabetes and obesity. We hypothesized that glycemia, insulin resistance, and waist circumference modulate these alterations in type 2 diabetes and, to a lesser extent, in individuals without type 2 diabetes.

Research Design And Methods: In 88 lean and obese subjects without and 40 with type 2 diabetes on an inpatient protein-controlled isoenergetic diet for 7 days, whole-body protein turnover was measured using the fed-fasted 60-h oral (15)N-glycine method.

The greater contribution of gluconeogenesis to glucose production in obesity is related to increased whole-body protein catabolism.

Obesity is associated with an increase in the fractional contribution of gluconeogenesis (GNG) to glucose production. We tested if this was related to the altered protein metabolism in obesity. GNG(PEP) (via phosphoenol pyruvate [PEP]) was measured after a 17-h fast using the deuterated water method and 2H nuclear magnetic resonance spectroscopy of plasma glucose.

The influence of sex on the protein anabolic response to insulin.

We hypothesize that sex influences whole-body protein anabolism in the postabsorptive state and in response to hyperinsulinemia. Kinetics of 3-(3)H-glucose and (13)C-leucine were studied in 16 men and 15 women after energy- and protein-controlled diets, before and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp. In the postabsorptive state, women had 20% higher rates of leucine Ra (protein breakdown) and nonoxidative Rd (synthesis) adjusted for fat-free mass than men but net leucine balance was as negative.

Whole-body protein anabolic response is resistant to the action of insulin in obese women.

Background: Obesity is associated with insulin resistance of glucose and lipid metabolism.

Objective: We sought to determine the effects of obesity on the insulin sensitivity of protein metabolism.

Design: Whole-body [(13)C]leucine and [(3)H]glucose kinetics were measured in 9 lean and 10 obese women in the postabsorptive state and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp.

Combined infusion of epinephrine and norepinephrine during moderate exercise reproduces the glucoregulatory response of intense exercise.

Intense exercise (IE) (>80% O(2max)) causes a seven- to eightfold increase in glucose production (R(a)) and a fourfold increase in glucose uptake (R(d)), resulting in hyperglycemia, whereas moderate exercise (ME) causes both to double. If norepinephrine (NE) plus epinephrine (Epi) infusion during ME produces the plasma levels and R(a) of IE, this would prove them capable of mediating these responses. Male subjects underwent 40 min of 53% O(2max) exercise, eight each with saline (control [CON]), or with combined NE + Epi (combined catecholamine infusion [CCI]) infusion from min 26-40.