Showing papers by "Darleen A. Sandoval published in 2003"
TL;DR: The purpose of this review to is critically analyze the literature regarding the impact of different types of stress on leptin secretion, the function of leptin during stress, and the role of leptin in the pathophysiology of diabetes.
Abstract: Leptin, a protein released from adipose tissue, is being recognized to play an integral role in endocrine regulation of metabolism. While it is clearly evident that leptin is decreased during caloric restriction, the response of leptin to other types of stress has been plagued by conflicting data. With hypoglycemia stress, the literature may conflict because experimentally hypoglycemia is induced with infusion of insulin, an endocrine factor that can increase leptin levels. With exercise, leptin's response may depend on duration and intensity of exercise. While it has been clearly shown that the sympathetic nervous system (SNS) inhibits leptin secretion in a variety of experimental modes, the hypothalamic-pituitary-adrenal (HPA) axis may stimulate leptin secretion. This creates a paradox of leptin regulation during stress since both systems are activated with stress. If the SNS inhibition overrides the HPA axis' activation of leptin secretion, leptin's role during stress may be to allow a shifting of fuel consumption towards carbohydrate utilization. In type 1 diabetes mellitus, autonomic dysfunction may prevent the fall in leptin during stress. Although obesity is associated with type 2 diabetes mellitus, patients may have decreased leptin levels, especially when glucose is poorly controlled. This may contribute to further obesity and worsening of the disease. The purpose of this review to is critically analyze the literature regarding the impact of different types of stress on leptin secretion, the function of leptin during stress, and the role of leptin in the pathophysiology of diabetes.
122 citations
TL;DR: It is concluded that estrogen appears to play a major role in the sexual dimorphism present in counterregulatory responses to hypoglycemia in healthy humans.
Abstract: This study tested the hypothesis that estrogen is the mechanism responsible for the sexual dimorphism present in the neuroendocrine and metabolic responses to hypoglycemia. Postmenopausal women receiving (E2; n = 8) or not receiving (NO E2; n = 9) estrogen replacement were compared with age- and BMI-matched male subjects (n = 8) during a single-step 2-h hyperinsulinemic-hypoglycemic clamp. Plasma insulin (599 +/- 28 pmol/l) and glucose (2.9 +/- 0.03 mmol/l) levels were similar among all groups during the glucose clamp. In response to hypoglycemia, epinephrine (2.8 +/- 0.6 vs. 5.8 +/- 0.8 and 4.4 +/- 0.5 nmol/l), glucagon (57 +/- 8 vs. 77 +/- 8 and 126 +/- 18 ng/l), and endogenous glucose production (2 +/- 2 vs. 10 +/- 2 and 6 +/- 3 micro mol x kg(-1) x min(-1)) were significantly lower in E2 vs. both NO E2 and male subjects (P < 0.05). These reduced counterregulatory responses resulted in significantly greater glucose infusion rates (16 +/- 2 vs. 6 +/- 2 and 6 +/- 3 micro mol x kg(-1) x min(-1); P < 0.01) in E2 vs. both NO E2 and male subjects. Pancreatic polypeptide was significantly lower (P < 0.05) in both the E2 and NO E2 groups compared with the male subjects (136 +/- 20 and 136 +/- 23 vs. 194 +/- 16 pmol/l). Last, glycerol (36 +/- 3 vs. 47 +/- 5 micro mol/l; P < 0.05), lactate (1.4 +/- 0.1 vs. 1.8 +/- 0.2 mmol/l; P < 0.05), and muscle sympathetic nerve activity (19 +/- 4 to 27 +/- 4 vs. 27 +/- 5 to 42 +/- 6 bursts/min; P < 0.05) responses to hypoglycemia were all significantly lower in E2 vs. NO E2 subjects. We conclude that estrogen appears to play a major role in the sexual dimorphism present in counterregulatory responses to hypoglycemia in healthy humans.
73 citations
TL;DR: It is concluded that cortisol can act directly on the central nervous system to blunt counterregulatory responses to subsequent hypoglycemia in the conscious rat.
Abstract: Physiological levels of cortisol have been found to blunt neuroendocrine and metabolic responses to subsequent hypoglycemia in humans. The aim of this study was to determine whether cortisol acts directly on the brain to elicit this effect. A total of 41 conscious unrestrained Sprague-Dawley rats were studied during 2-day experiments. Day 1 consisted of two episodes of clamped 2-h hyperinsulinemic (30 pmol · kg −1 · min −1 ) hypoglycemia (2.8 ± 0.1 mmol/l; n = 12; ANTE HYPO), euglycemia (6.2 ± 0.1 mmol/l; n = 12; ANTE EUG), or euglycemia (6.2 ± 0.1 mmol/l) plus simultaneous intracerebroventricular (ICV) infusion of cortisol (25 μg/h; n = 9; ANTE EUG+Cort) or saline (24 μl/h; n = 8; ANTE EUG+Sal). For all groups, day 2 consisted of a 2-h hyperinsulinemic (30 pmol · kg −1 · min −1 ) hypoglycemic (2.9 ± 0.2 mmol/l) clamp. Plasma epinephrine and glucagon incremental area under the curve (ΔAUC) responses were significantly less in ANTE EUG+Cort and ANTE HYPO versus both ANTE EUG and ANTE EUG+Sal ( P P P P
34 citations
TL;DR: Plasma leptin levels decrease in response to hypoglycemia in healthy but not type 1 diabetes mellitus subjects, however, T1DM patients do have increased basal leptin levels compared to healthy man.
Abstract: These studies examined the effects of hypoglycemia or exercise on leptin levels in 47 (23 women, 24 men) healthy (age 26±2 years, body mass index 23±0.5 kg·m −2 ) and type 1 diabetes mellitus (T1DM) subjects (age 29±2 years, body mass index 27±2 kg·m −2 ). In Study 1, healthy and T1DM subjects were exposed to morning and afternoon 120-min hyperinsulinemic hypoglycemic (∼50 mg/dl) or euglycemic (∼90 mg/dl) clamps. In Study 2, healthy subjects were studied during morning and afternoon 90-min exercise bouts at 50% VO 2max . In Study 1, basal levels of leptin were significantly greater in T1DM vs. the healthy subjects (13.8±3 vs. 5.4±1 ng/dl; P P P
10 citations
TL;DR: The presence of circulating estradiol and progesterone during the PILL phase reduces glucose and lactate responses to hypoxic exercise.
Abstract: To test whether the oral contraceptive pill cycle affects endocrine and metabolic responses to hypoxic (fraction of inspired oxygen = 13%, P(IO2): 95 mmHg; H) versus normoxic (P(IO2):153 mmHg; N) exercise, we examined eight women (28 +/- 1.2 yr) during the third (PILL) and placebo (PLA) weeks of their monthly oral contraceptive pill cycle. Cardiopulmonary, metabolic, and neuroendocrine measurements were taken before, during, and after three 5-min consecutive workloads at 30%, 45%, and 60% of normoxic V(O2peak) in H and N trials. Heart rate response to exercise was greater in H versus N, but was not different between PILL and PLA. Lactate levels were significantly greater during exercise, and both lactate and glucose levels were significantly greater for 30 min after exercise in H versus N (p < 0.0001). When expressed relative to baseline, lactate levels were lower in PILL versus PLA, but glucose was greater in PILL versus PLA (p < 0.001). Cortisol levels were also significantly greater in PILL versus PLA (p < 0.001). Norepinephrine levels were significantly increased during exercise (p < 0.0001) and in H versus N (p < 0.0001). However, epinephrine levels were not different over time or with trial. Thus, the presence of circulating estradiol and progesterone during the PILL phase reduces glucose and lactate responses to hypoxic exercise.
4 citations