Enrichment, characterisation and in vivo\textit {in vivo} evaluation of single-chain-antibody fragments against surface proteins of the beta-cells

Der autoimmun-bedingte progrediente Verlust der pankreatischen, Insulin- produzierenden Beta-Zellen ist die zentrale Ursache für die Entstehung des Typ 1-Diabetes. Bei Patienten mit Typ 2-Diabetes tritt im Verlauf der Erkrankung ebenfalls eine Reduktion der BZM ($\underline {B}eta \underline {Z}ell \underline {M}asse$ auf, die durch eine erhöhte Apoptoserate bedingt zu sein scheint (Weier $\textit {et al}$., 1990; Butler $\textit {et al}$., 2003). Daraus resultiert, dass alle Typ 1-Diabetiker, aber auch viele betroffene Typ 2-Diabetiker im Verlauf der Erkrankung eine Insulintherapie durchführen müssen. Mit keiner verfügbaren Therapie (z.B. Insulin, orale Antidiabetika) ist es weder beim Typ 1- noch beim Typ 2-Diabetes bisher kausal gelungen, den Verlust der BZM aufzuhalten. Diese pathophysiologischen Zusammenhänge haben zu dem Bedürfnis geführt, die BZM nicht-invasiv $\textit {in vivo}$ beim Menschen zu bestimmen

Diminished glucagon suppression after β-cell reduction is due to impaired α-cell function rather than an expansion of α-cell mass

Impaired suppression of glucagon levels after oral glucose or meal ingestion is a hallmark of type 2 diabetes. Whether hyperglucagonemia after a β-cell loss results from a functional upregulation of glucagon secretion or an increase in α-cell mass is yet unclear. CD-1 mice were treated with streptozotocin (STZ) or saline. Pancreatic tissue was collected after 14, 21, and 28 days and examined for α- and β-cell mass and turnover. Intraperitoneal (ip) glucose tolerance tests were performed at day 28 as well as after 12 days of subcutaneous insulin treatment, and glucose, insulin, and glucagon levels were determined. STZ treatment led to fasting and post-challenge hyperglycemia (P < 0.001 vs. controls). Insulin levels increased after glucose injection in controls (P < 0.001) but were unchanged in STZ mice (P = 0.36). Intraperitoneal glucose elicited a 63.1 ± 4.1% glucagon suppression in control mice (P < 0.001), whereas the glucagon suppression was absent in STZ mice (P = 0.47). Insulin treatment failed to normalize glucagon levels. There was a significant inverse association between insulin and glucagon levels after ip glucose ingestion (r2 = 0.99). β-Cell mass was reduced by ∼75% in STZ mice compared with controls (P < 0.001), whereas α-cell mass remained unchanged (P > 0.05). α-Cell apoptosis (TUNEL) and replication (Ki67) were rather infrequently noticed, with no significant differences between the groups. These studies underline the importance of endogenous insulin for the glucose-induced suppression of glucagon secretion and suggest that the insufficient decline in glucagon levels after glucose administration in diabetes is primarily due to a functional loss of intraislet inhibition of α-cell function rather than an expansion of α-cell mass

Role of child maltreatment and gender for bipolar symptoms in young adults

$\bf Background$ Child maltreatment has been shown to be associated with a wide range of mental disorders, including bipolar disorders. In this 2-year follow-up study, recollections of emotional, physical and sexual abuse were related to bipolar symptoms, namely depressive, hypomanic and manic symptoms. $\bf Methods$ The sample consists of 134 students who took part at five measurement times within the 2-year period. Data were collected with self-report scales. $\bf Results$ The results show that recollections of abuse, particularly emotional abuse, were associated with more severe depressive symptoms; this finding, however, only applied to women. Hypomanic and manic symptoms were not associated with recollections of abuse. For hypomanic symptoms, however, a significant decrease over the 2 years was observed. $\bf Conclusions$ The findings of this study suggest that recollections of abusive experiences in childhood combined with female gender increase the risk for depression, whereas hypomanic and manic states are probably better predicted by other factors, such as current life circumstances