Doxepin therapy for postprandial symptomatic hypoglycaemic patients: neurochemical, hormonal and metabolic disturbances

1991 ◽  
Vol 80 (4) ◽  
pp. 373-384 ◽  
Author(s):  
Fuad Lechin ◽  
Bertha van der Dijs ◽  
Alex Lechin ◽  
Marcel Lechin ◽  
Eduardo Coll-García ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Tension Headache ◽  
Plasma Noradrenaline ◽  
Oral Glucose ◽  
Type I ◽  
Glucose Load ◽  
Metabolic Disturbances ◽  
Type Iii ◽  
Glucose Levels ◽  
Basal Plasma

1. Three oral glucose tolerance tests were performed in each of 32 symptomatic postprandial hypoglycaemic patients (before placebo, before doxepin therapy and after doxepin therapy). Plasma neurotransmitters were determined in parallel with assays of plasma insulin and glucose levels. 2. Three different types of patients were distinguished. Type I showed a low noradrenaline/adrenaline ratio, high dopamine levels and low platelet 5-hydroxytryptamine (serotonin) levels during basal periods. After a glucose load, late peaks of dopamine and free 5-hydroxytryptamine, which coincided with the symptoms but not with the nadir of plasma glucose, were observed. Type II showed a low basal plasma noradrenaline/adrenaline ratio. After a glucose load, progressive increases in adrenaline and decreases in glucose were seen. Adrenergic symptoms coincided with the nadir of glucose. Although type III patients showed hyperinsulinaemia after a glucose load similar to the other types of patient, they did not show hyperglycaemia, but rather exhibited a sustained and progressive reduction in plasma glucose. These patients were characterized by a high basal plasma noradrenaline/adrenaline ratio, high basal plasma levels of 4-hydroxy-3-methoxyphenylethyleneglycol and high basal levels of platelet 5-hydroxytryptamine, all of which increased after a glucose load. Systolic and diastolic blood pressure decreases paralleled reductions in heart rate and glucose. The nadir of plasma glucose occurred simultaneously with the appearance of symptoms (weakness, heartburn, oppressive chest pain, tension headache, abdominal cramps, dizziness, etc.). Therapy with doxepin led to disappearance of the symptoms within 3–4 weeks. Normalization of all other disordered variables (cardiovascular, metabolic and neurochemical, and the clonidine test) paralleled the disappearance of the symptoms. 3. Symptoms varied in the three types of patients and we conclude that they are related to hypoglycaemia-induced disorders of plasma neurotransmitters, rather than to hypoglycaemia per se. We postulate that an uncoping stress situation (type I and II patients) and depression (type III patients) underlie the physiopathological mechanisms.

scholarly journals Lean mass inversely predicts plasma glucose levels after oral glucose load independent of insulin secretion or insulin sensitivity in glucose intolerance subjects

2014 ◽  
Vol 61 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Jirateep Kwankaew ◽  
Sunee Saetung ◽  
Suwannee Chanprasertyothin ◽  
Rattana Leelawattana ◽  
Chatchalit Rattarasarn
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Intolerance ◽  
Lean Mass ◽  
Plasma Glucose ◽  
Oral Glucose ◽  
Oral Glucose Load ◽  
Glucose Load ◽  
Glucose Levels

scholarly journals Prevention of Postprandial Hyperglycemia by Ophthalmic Nanoparticles Based on Protamine Zinc Insulin in the Rabbit

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 375
Author(s):  
Saori Deguchi ◽  
Fumihiko Ogata ◽  
Takumi Isaka ◽  
Hiroko Otake ◽  
Yosuke Nakazawa ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Plasma Glucose ◽  
Polyacrylic Acid ◽  
Rabbit Model ◽  
Postprandial Hyperglycemia ◽  
Postprandial Blood Glucose ◽  
Oral Glucose ◽  
Glucose Levels ◽  
Protamine Zinc Insulin ◽  
Bead Mill

Postprandial hyperglycemia, a so-called blood glucose spike, is associated with enhanced risks of diabetes mellitus (DM) and its complications. In this study, we attempted to design nanoparticles (NPs) of protamine zinc insulin (PZI) by the bead mill method, and prepare ophthalmic formulations based on the PZI-NPs with (nPZI/P) or without polyacrylic acid (nPZI). In addition, we investigated whether the instillation of the newly developed nPZI and nPZI/P can prevent postprandial hyperglycemia in a rabbit model involving the oral glucose tolerance test (OGTT). The particle size of PZI was decreased by the bead mill to a range for both nPZI and nPZI/P of 80–550 nm with no observable aggregation for 6 d. Neither nPZI nor nPZI/P caused any noticeable corneal toxicity. The plasma INS levels in rabbits instilled with nPZI were significantly higher than in rabbits instilled with INS suspensions (commercially available formulations, CA-INS), and the plasma INS levels were further enhanced with the amount of polyacrylic acid in the nPZI/P. In addition, the rapid rise in plasma glucose levels in OGTT-treated rabbits was prevented by a single instillation of nPZI/P, which was significantly more effective at attenuating postprandial hyperglycemia (blood glucose spike) in comparison with nPZI. In conclusion, we designed nPZI/P, and show that a single instillation before OGTT attenuates the rapid enhancement of plasma glucose levels. These findings suggest a better management strategy for the postprandial blood glucose spike, which is an important target of DM therapy.

Insulin and glucagon in rats with Islet cell tumors Induced by small doses of streptozofoclii

1981 ◽  
Vol 59 (8) ◽  
pp. 818-823 ◽  
Author(s):  
Gen Yoshino ◽  
Tsutomu Kazumi ◽  
Soichiro Morita ◽  
Shighaki Baba
Keyword(s):  
Plasma Glucose ◽  
Islet Cell ◽  
Insulin Response ◽  
Oral Glucose ◽  
Islet Cell Tumors ◽  
Glucose Levels ◽  
Tumor Bearing ◽  
Small Doses ◽  
Wet Weight ◽  
Glucose Plasma

Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma glucagon levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 ± 8.60 and 35.07 ± 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 ± 0.61 and 2.24 ± 0.67 μg/g wet weight, respectively).These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.

scholarly journals Oral Glucose Augments the Counterregulatory Hormone Response during Insulin-Induced Hypoglycemia in Humans1

2001 ◽  
Vol 86 (2) ◽  
pp. 645-648
Author(s):  
Rubina A. Heptulla ◽  
William V. Tamborlane ◽  
Tony Y.-Z. Ma ◽  
Fran Rife ◽  
Robert S. Sherwin.
Keyword(s):  
Plasma Glucose ◽  
Animal Studies ◽  
Healthy Adult ◽  
Systemic Circulation ◽  
Glucose Sensors ◽  
Oral Glucose ◽  
Adult Males ◽  
Hormone Response ◽  
Glucose Levels ◽  
Acute Hypoglycemia

It has been suggested that the counterregulatory hormone (CRH) response to acute hypoglycemia is triggered via glucose sensors situated in either the hypothalamus or the portohepatic area. If the latter were critical during hypoglycemia, one would anticipate that ingestion of glucose, by raising glucose levels in the portal circulation, should attenuate CRH responses previously described in animal studies. To evaluate the effect of raising portal, but not peripheral, glucose levels during insulin-induced hypoglycemia, we performed hypoglycemic clamp studies in five healthy adult males on two occasions. On one occasion, subjects received oral glucose (OG) (25 g) during hypoglycemia; and on one occasion, noncarbohydrate-containing drink of equal volume, while maintaining plasma glucose at 55 ± 2 mg/dL (3.08 mmol/L). As a result, there were no significant differences in systemic plasma glucose levels between the two hypoglycemic clamp studies, and basal CRH concentrations were also similar. As expected, there was a brisk rise in all CRH during the control (hypoglycemia+noncarbohydrate drink) study. In the experimental study, administration of OG (hypoglycemia+OG), to raise intraportal glucose levels during systemic hypoglycemia, did not attenuate CRH responses. Indeed, OG enhanced the rise in epinephrine, glucagon, and GH. Increases in cortisol and norepinephrine did not differ between the two studies. Therefore, our data suggest that increasing the level of glucose in the portal vein above that in the systemic circulation, during hypoglycemia, enhances (rather than suppresses) CRH responses. Thus, ingestion of glucose may reverse hypoglycemia directly by provision of substrate, as well as indirectly by stimulating counteregulatory mechanisms.

Acute Effect of Chili Consumption on Thermogenesis and Glycemic Response Following Oral Glucose Load in Men

2020 ◽  
Vol 19 (3) ◽  
pp. 288-294
Author(s):  
Muriel Ávila-Seguel ◽  
Constanza Márquez-Urrizola ◽  
Gislaine Granfeldt ◽  
Katia Saez-Carrillo ◽  
Javad Sharifi-Rad ◽  
...  
Keyword(s):  
Acute Effect ◽  
Chili Pepper ◽  
Oral Glucose ◽  
Glycemic Response ◽  
Oral Glucose Load ◽  
Glucose Load ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Post Test ◽  
Quasi Experimental

Hypoglycemic and thermogenic effects are attributed to the capsaicinoid compounds (capsaicin). The aim of this study was to evaluate the acute effect of the consumption of 5g of chili pepper on thermogenesis and the glycemic response. In a pretest-post-test quasi-experimental study, the energy expenditure (EE) of 15 healthy men was evaluated by using indirect calorimetry at rest and with the consumption of 5g of Capsicum annum. In addition, the glycemic response after an oral glucose load was evaluated. After the consumption of C. annum, there was a significant increase in the EE of all the participants during the first few seconds postchili consumption. In sedentary participants, the consumption of chili pepper caused a significant decrease of blood glucose levels. The consumption of chili pepper has a potential immediate thermogenic effect during the first few seconds and, in sedentary people, it has a potential hypoglycemic effect.

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