Medicinal plants of India with anti-diabetic potential.

The modern era of neuroendocrinology was ushered in just over a decade ago with the isolation and characterization, from ovine1 and porcine2 hypothalamic tissue, of a tripeptide (pyroglutamyl-histi...

Thyrotropin-releasing hormone

Increasing use of assays for TSH with improved sensitivity as a first-line test of thyroid function has raised questions regarding prevalence and clinical significance of abnormal results, especially values below normal. We have assessed the thyroid status of 1210 patients aged over 60 registered with a single general practice by measurement of serum TSH using a sensitive assay. High TSH values were more common in females (11.6%) than males (2.9%). TSH values below normal were present in 6.3% of females and 5.5% of males, with values below the limit of detection of the assay present in 1.5% of females and 1.4% of males. Anti-thyroid antibodies were found in 60% of those with high TSH but only 5.6% of those with subnormal TSH. Eighteen patients were hypothyroid (high TSH, low free thyroxine) and one thyrotoxic (low TSH, raised free thyroxine) at initial testing. Seventy-three patients with elevated TSH but normal free T4 were followed for 12 months; 13 (17.8%) developed low free T4 levels and commenced thyroxine, TSH returned to normal in four (5.5%) and 56 (76.7%) continued to have high TSH values. Sixty-six patients with TSH results below normal were followed. Of the 50 subjects with low but detectable TSH at initial testing, 38 (76%) returned to normal at 12 months; of those 16 with undetectable TSH followed, 14 (87.5%) remained low at 12 months. Only one subject (who had an undetectable TSH) developed thyrotoxicosis. In view of the marked prevalence of thyroid dysfunction in the elderly, we suggest that screening of all patients over 60 should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom

Acetylcholine (ACh), the major parasympathetic neurotransmitter, is released by intrapancreatic nerve endings during the preabsorptive and absorptive phases of feeding. In beta-cells, ACh binds to muscarinic M(3) receptors and exerts complex effects, which culminate in an increase of glucose (nutrient)-induced insulin secretion. Activation of PLC generates diacylglycerol. Activation of PLA(2) produces arachidonic acid and lysophosphatidylcholine. These phospholipid-derived messengers, particularly diacylglycerol, activate PKC, thereby increasing the efficiency of free cytosolic Ca(2+) concentration ([Ca(2+)](c)) on exocytosis of insulin granules. IP3, also produced by PLC, causes a rapid elevation of [Ca(2+)](c) by mobilizing Ca(2+) from the endoplasmic reticulum; the resulting fall in Ca(2+) in the organelle produces a small capacitative Ca(2+) entry. ACh also depolarizes the plasma membrane of beta-cells by a Na(+)- dependent mechanism. When the plasma membrane is already depolarized by secretagogues such as glucose, this additional depolarization induces a sustained increase in [Ca(2+)](c). Surprisingly, ACh can also inhibit voltage-dependent Ca(2+) channels and stimulate Ca(2+) efflux when [Ca(2+)](c) is elevated. However, under physiological conditions, the net effect of ACh on [Ca(2+)](c) is always positive. The insulinotropic effect of ACh results from two mechanisms: one involves a rise in [Ca(2+)](c) and the other involves a marked, PKC-mediated increase in the efficiency of Ca(2+) on exocytosis. The paper also discusses the mechanisms explaining the glucose dependence of the effects of ACh on insulin release.

Mechanisms and Physiological Significance of the Cholinergic Control of Pancreatic β-Cell Function

Optimal digestion and absorption of nutrients requires a complex interaction among motor and secretory functions of the gastrointestinal tract. Digestion of macronutrients is a prerequisite for absorption and occurs mostly via enzymatic hydrolysis. In this context, pancreatic enzymes, in particular lipase, amylase, trypsin, and chymotrypsin, play the most important role but several brush border enzymes as well as other pancreatic and extrapancreatic enzymes also participate in macronutrient digestion. The crucial importance of pancreatic exocrine function is reflected by the detrimental malabsorption in patients with untreated pancreatic exocrine insufficiency, which is a typical complication of, for example, chronic pancreatitis.1–4

Comprehensive knowledge about the physiological pancreatic exocrine response to normal diets and to individual food components and about alterations in pancreatic exocrine insufficiency is necessary to administer a pancreatic enzyme preparation which imitates physiological conditions closely. Although many efforts have been made to substitute for pancreatic exocrine insufficiency by specially designed pancreatic enzyme preparations, these still have several disadvantages compared with physiological enzyme secretion. In particular lipid absorption is not completely normalised in most patients.5

As a basis for a better understanding of pancreatic exocrine function in health and disease this review will first summarise literature data on pancreatic exocrine response to a normal diet and to administration of individual food components in healthy humans. The next chapter will focus on pancreatic responses to a normal diet and to administration of individual food components in patients with pancreatic diseases, in particular chronic pancreatitits, but also in patients with other pancreatic and non-pancreatic diseases which are associated with intraluminal lack of pancreatic enzymes, for instance coeliac disease and diabetes mellitus. Other evidence of pancreatic involvement and dysfunction in these diseases will also be discussed, particularly if sufficient data on endogenously stimulated pancreatic secretion are lacking.

### 2.1 Introduction

The healthy human pancreas adopts …

https://gut.bmj.com/content/gutjnl/54/suppl_6/1.full.pdf

Human pancreatic exocrine response to nutrients in health and disease.

The influences of glucocorticoid administration or increased serum corticoid concentration on TRF-induced TSH release was studied in patients receiving glucocorticoids and in patients with Cushing's syndrome. The TRFinduced TSH release was inhibited in patients who had received glucocorticoids for long periods or in high doses. These patients had received more than 60 mEq of cortisol per day for more than six months. Definite plasma TSH increases by TRF were observed in patients receiving shortterm, low doses or intermittent, low doses administration of glucocorticoid. Little or no rise of plasma TSH occurred following TRF administration to patients with Cushing's syndrome. From these observations it is possible to conclude that the mechanism of the glucocorticoid suppressive action on TSH secretion after short-term, low doses of glucocorticoid administration may be an impaired secretion of endogenous TRF, which results in a supernormal TSH response induced by exogenous TRF. With long-term and high doses ...

Influence of glucocorticoids on TRF-induced TSH response in man.

We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr. The contents of pancreatic protein, DNA, and digestive enzymes were markedly reduced after the arginine injection and reached their nadirs at 72 hr. After 14 days these levels were almost normal. Histologic examination revealed a number of small vesicles within acinar cells at 6 hr, which were identified as markedly swollen mitochondria by the electron microscope. Other intracellular organelles and nuclei also showed degenerative changes. At 12 hr interstitial edema appeared, and acinar cell necrosis was seen after 24 hr. The extent and severity of necrotic changes of pancreatic exocrine tissue with inflammatory cell infiltration were maximal at 72 hr. At seven days, pancreatic acinar cells began to regenerate, and pancreatic architecture appeared almost normal after 14 days. The present study has demonstrated that the administration of excessive doses of arginine induces a new, noninvasive experimental model of acute necrotizing pancreatitis.

New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats.

We studied the histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation in rats. All rats received 4 subcutaneous injections of various doses of caerulein (5–50 μg/kg body weight) at hourly intervals over 3 h, and 9 h after the first injection all animals were killed. Subcutaneous injections of 20 μg/kg body weight of caerulein induced a significant increase in serum amylase activity and histologic evidence of acute interstitial pancreatitis similar to those observed with the 50 μg/kg body weight dosage of caerulein. Therefore, a total of 4 subcutaneous injections of 20 μg/kg body weight of caerulein was chosen to study the time-course of structural and biochemical alterations in caerulein-induced acute pancreatitis. Serum amylase activity reached a maximal value of 10-fold increase over the basal values at 6 h, and then decreased gradually to normal values at 18 h after the first injection. Remarkable interstitial edema and cytoplasmic vacuoles in acinar cells were the earliest histologic alterations. Cellular infiltration was prominent at 9–12 h after the first injection. Although these histologic changes almost completely disappeared after 24 h, the reduction in the number of zymogen granules was still detectable by electron microscopic examination even after 7 days. DNA content in the pancreas showed no significant changes following the induction of acute pancreatitis, whereas a moderate to marked reduction in enzyme content persisted after 7 days. Within 14 days after the initiation of the injections, both structural and biochemical changes had completely disappeared. *** DIRECT SUPPORT *** A00DX035 00005

Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation

Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats

Although elevated amylase levels in serum, pleural fluid, and extracts of tumor tissue in primary lung cancer have been reported, electrophoretic and column-chromatographic studies have not revealed the ectopic production of amylase but have merely shown an increase of amylase activity of chiefly the salivary type in these materials The present study was designed to make clear the nature of the amylase or amylase-like substance in the serum, pleural fluid and tumor extracts, and to determine whether amylase might be produced ectopically in tumor tissues Our data not only confirmed that the hyperamylasemia in some cases of primary lung cancer was due to an increase in salivary type isoamylases, but also showed that the same isoamylase pattern occurs in serum, pleural fluids, and diseased lung tissue of patients with pneumonia However, the elution pattern of amylase in these materials in column-chromatography on Sephadex G-75 Superfine was different from that of salivary amylase On the basis of our observations, it seems reasonable to conclude that the salivary type hyperamylasemia in some cases of primary lung cancer may be due to an increase in the amylase contained in normal lung tissues, resulting from activation and release into the blood stream by some inflammatory process However, ectopic production of amylase was demonstrated in one particular case of primary lung cancer in which a high amylase content and a peculiar isoamylase were found both in the primary and metastatic lesions

Makoto Otsuki

Papers

Influence of glucocorticoids on TRF-induced TSH response in man.

New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats.

Histologic and biochemical alterations in experimental acute pancreatitis induced by supramaximal caerulein stimulation

Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats

Amylase in the lung.