The effect of insulin on in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans.

The continuous delivery of glucose to the brain is critically important to the maintenance of normal metabolic function. However, elucidation of the hormonal regulation of in vivo cerebral glucose metabolism in humans has been limited by the lack of direct, noninvasive methods with which to measure brain glucose. In this study, we sought to directly examine the effect of insulin on glucose concentrations and rates of glucose transport/metabolism in human brain using (1)H-magnetic resonance spectroscopy at 4 Tesla. Seven subjects participated in paired hyperglycemic (16.3 +/- 0.3 mmol/l) clamp studies performed with and without insulin. Brain glucose remained constant throughout (5.3 +/- 0.3 micromol/g wet wt when serum insulin = 16 +/- 7 pmol/l vs. 5.5 +/- 0.3 micromol/g wet wt when serum insulin = 668 +/- 81 pmol/l, P = NS). Glucose concentrations in gray matter-rich occipital cortex and white matter-rich periventricular tissue were then simultaneously measured in clamps, where plasma glucose ranged from 4.4 to 24.5 mmol/l and insulin was infused at 0.5 mU. kg(-1). min(-1). The relationship between plasma and brain glucose was linear in both regions. Reversible Michaelis-Menten kinetics fit these data best, and no differences were found in the kinetic constants calculated for each region. These data support the hypothesis that the majority of cerebral glucose uptake/metabolism is an insulin-independent process in humans.

Effect of protein ingestion on the glucose appearance rate in people with type 2 diabetes.

Amino acids derived from ingested protein are potential substrates for gluconeogenesis. However, several laboratories have reported that protein ingestion does not result in an increase in the circulating glucose concentration in people with or without type 2 diabetes. The reason for this has remained unclear. In people without diabetes it seems to be due to less glucose being produced and entering the circulation than the calculated theoretical amount. Therefore, we were interested in determining whether this also was the case in people with type 2 diabetes. Ten male subjects with untreated type 2 diabetes were given, in random sequence, 50 g protein in the form of very lean beef or only water at 0800 h and studied over the subsequent 8 h. Protein ingestion resulted in an increase in circulating insulin, C-peptide, glucagon, alpha amino and urea nitrogen, and triglycerides; a decrease in nonesterified fatty acids; and a modest increase in respiratory quotient. The total amount of protein deaminated and the amino groups incorporated into urea was calculated to be approximately 20-23 g. The net amount of glucose estimated to be produced, based on the quantity of amino acids deaminated, was approximately 11-13 g. However, the amount of glucose appearing in the circulation was only approximately 2 g. The peripheral plasma glucose concentration decreased by approximately 1 mM after ingestion of either protein or water, confirming that ingested protein does not result in a net increase in glucose concentration, and results in only a modest increase in the rate of glucose disappearance.

The use of the hypoglycaemic clamp in the assessment of pituitary function.

OBJECTIVE: The standard dynamic test used to diagnose hypopituitarism is the insulin tolerance test (ITT), in which insulin-induced secretion of ACTH, GH and cortisol is measured. However, because of differences in insulin sensitivity some patients fail achieve sufficient hypoglycaemia to assess pituitary function and colleagues experience severe hypoglycaemia and are at risk for cardiac dysrhythmia, seizure or coma. This risk may be particularly pertinent in the evaluation of older adults. We hypothesized that the hypoglycaemic clamp may be useful in assessing pituitary function in some patients. PATIENTS AND MEASUREMENTS: Twenty-one normal subjects (14 old [50-76 years] and 7 young [18-36 years]) and 7 hypopituitary subjects were studied. A clamp study was performed in which insulin infusion was given at 2 mU/kg/min and increased to 4 mU/kg/min if the target glucose concentration was not reached after 40 min. Dextrose was infused as needed to clamp the plasma glucose concentration at 2.2 mmol/l for 30 min. On a separate day, 7 young controls also underwent an ITT in which 0.15 U/kg insulin was administered as a bolus intravenous injection at time 0. In both studies, baseline values were taken at - 10, - 5 and 0 min. Samples were then collected every 5 min for plasma glucose and every 10 min for insulin, ACTH, cortisol and GH. RESULTS: ACTH and GH secretion during each test were similar in younger controls (P = NS) but cortisol secretion was lower during ITT (P < 0.01 vs. clamp). Hypopituitary subjects had significantly less ACTH, cortisol and GH secretion than controls of all ages (P < 0.001 for all). Peak GH secretion was significantly lower in the old controls than in young controls (22 +/- 12 vs. 48 +/- 26 mU/l, respectively; P < 0.01) but significantly higher than the hypopituitary subjects (2 +/- 2 mu/l; P < 0.001). CONCLUSION: These data demonstrate that the hypoglycaemic clamp can be used in the assessment of pituitary function and suggest that this technique may be particularly beneficial in the evaluation of GH deficiency in older adults who may not tolerate the ITT.